Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure ...Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.展开更多
It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular ...It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.展开更多
Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or dela...Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.展开更多
The onset of inflammatory bowel disease(IBD)involves many factors,including environmental parameters,microorganisms,and the immune system.Although research on IBD continues to expand,the specific pathogenesis mechanis...The onset of inflammatory bowel disease(IBD)involves many factors,including environmental parameters,microorganisms,and the immune system.Although research on IBD continues to expand,the specific pathogenesis mechanism is still unclear.Protein modification refers to chemical modification after protein biosynthesis,also known as post-translational modification(PTM),which causes changes in the properties and functions of proteins.Since proteins can be modified in different ways,such as acetylation,methylation,and phosphorylation,the functions of proteins in different modified states will also be different.Transitions between different states of protein or changes in modification sites can regulate protein properties and functions.Such modifications like neddylation,sumoylation,glycosylation,and acetylation can activate or inhibit various signaling pathways(e.g.,nuclear factor-κB(NF-κB),extracellular signal-regulated kinase(ERK),and protein kinase B(AKT))by changing the intestinal flora,regulating immune cells,modulating the release of cytokines such as interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ),and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier.In this review,we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.展开更多
Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging...Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging and the resulting protein often suffers from significantly reduced yield and activity.Here we used genetic code expansion technique to introduce a surface exposed self-paired dithiol functional group into proteins,which can be selectively reduced to afford active thiols.Two compounds containing self-paired disulfides were synthesized,and their genetic incorporations were validated using green fluorescent proteins(GFP).The compatibility of these self-paired di-thiols with natural disulfide bond was demonstrated using antibody fragment to afford site-specifically labeled antibody.This work provides another valuable building block into the chemical tool-box for site-specific labeling of proteins containing internal disulfides.展开更多
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
This study investigated the integrated atlas of protein phosphorylation,acetylation,ubiquitination and S-nitrosylation in pre-rigor(0.5 h)and post-rigor(5 days)lamb to interpret the roles of protein posttranslational ...This study investigated the integrated atlas of protein phosphorylation,acetylation,ubiquitination and S-nitrosylation in pre-rigor(0.5 h)and post-rigor(5 days)lamb to interpret the roles of protein posttranslational modifications(PTMs)during meat aging.The results showed that the most common PTMs in postmortem meat were phosphorylated proteins.PTMs regulation during the postmortem period altered proteins involved in metabolic pathways and muscle contraction.The phosphorylation and ubiquitination of proteins located in mitochondria and nuclear changed significantly between 0.5 h and 5 days postmortem.Gene set enrichment analysis revealed possible roles of total PTMs proteins,with a general downregulation of phosphorylation,acetylation and ubiquitination.There was a weak correlation in the lysine PTM of acetylation and ubiquitination at the same site in postmortem meat.Multiple PTMs of proteins in glycolysis,TCA cycle,muscle contraction and the calcium signaling pathway cooperatively regulate meat quality development from pre-rigor to post-rigor.展开更多
Signal pathways participate in vital biological processes and regulate complex life activities through protein modifications.Protein modifications in signal pathways are accompanied by electron transfer.The study of e...Signal pathways participate in vital biological processes and regulate complex life activities through protein modifications.Protein modifications in signal pathways are accompanied by electron transfer.The study of electronic behavior helps to explore the physical and chemical processes in signal pathways,receiving extensive attention.There are some excellent reviews that have summarized methods for signal pathway detection,while few discussions are from an electron transfer perspective.This review describes the relationship between signal pathways and electron transfer in protein modification.Subsequently,we summarize the electron transfer-based detection methods,such as electrochemical,photoelectrochemical and electrochemiluminescence methods.Additionally,the applications of signal pathway detection in mechanism study and imaging are also reviewed.Finally,a comprehensive discussion of the summary and outlooks in this field is presented,aiming to provide valuable guidance for the molecular mechanism of life processes and the development of new analytical techniques.展开更多
Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products.Histone deacetylase(HDAC)inhibitors play an important role in the regulation of histone modifications in fu...Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products.Histone deacetylase(HDAC)inhibitors play an important role in the regulation of histone modifications in fungi,but their roles in prokaryotes remain poorly understood.Here,we investigated the global effects of the HDAC inhibitor,sodium butyrate(SB),on marine-derived Streptomyces olivaceus FXJ 8.021,particularly focusing on the activation of secondary metabolite biosynthesis.The antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters(BGCs)in strain FXJ 8.021,among which the silent lobophorin BGC was activated by SB.Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis(ge00097–ge00139)and CoA-ester formation(e.g.,ge02824),as well as the glycolysis/gluconeogenesis pathway(e.g.,ge01661),was significantly up-regulated in the presence of SB.Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester,thereby increasing the precursor supply for lobophorin biosynthesis.Further acetylomic analysis revealed that the acetylation levels on 218 sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated.These acetylated proteins were particularly enriched in transcriptional and translational machinery components(e.g.,elongation factor GE04399),and their correlations with the proteins involved in lobophorin biosynthesis were established by protein–protein interaction network analysis,suggesting that SB might function via a complex hierarchical.展开更多
Timely removal of oxidatively damaged proteins is crit- ical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein ...Timely removal of oxidatively damaged proteins is crit- ical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modifi- cation that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 （deleted in split hand/split foot 1）, an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSSl-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin- proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as amodifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.展开更多
Numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological chemistry.Approaches for site-specific modification of native amino ...Numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological chemistry.Approaches for site-specific modification of native amino acid residues in test tubes and biological contexts represent novel biological tools for understanding the role of peptides and proteins.Selective N-terminal modification strategies have been broadly studied especially in the last 10 years,as N-terminal positions are typically solvent exposed and provide chemically distinct sites for many peptide and protein targets,making N terminus distinct from other functional groups.A growing number of chemical and enzymatic techniques have been developed to modify N-terminal amino acids,and those techniques have the potential in the fields of medicine,basic research and applied materials science.This review focuses on appraising modification methodologies with the potential for biological applications from the past 10 years.展开更多
Post-translational modifications（PTMs） occurring at protein lysine residues,or protein lysine modifications（PLMs）,play critical roles in regulating biological processes.Due to the explosive expansion of the amount...Post-translational modifications（PTMs） occurring at protein lysine residues,or protein lysine modifications（PLMs）,play critical roles in regulating biological processes.Due to the explosive expansion of the amount of PLM substrates and the discovery of novel PLM types,here we greatly updated our previous studies,and presented a much more integrative resource of protein lysine modification database（PLMD）.In PLMD,we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs,including ubiquitination, acetylation, sumoylation, methylation ,succinylation,malonylation,glutarylation,giycation,formylation,hydroxylation,butyrylation,propionylation,crotonylation,pupylation,neddylation,2-hydroxyisobutyrylation,phosphoglycerylation,carboxylation,lipoylation and biotinylation.Using the data set,a motif-based analysis was performed for each PLM type,and the results demonstrated that different PLM types preferentially recognize distinct sequence motifs for the modifications.Moreover,various PLMs synergistically orchestrate specific cellular biological processes by mutual crosstalks with each other,and we totally found 65,297 PLM events involved in 90 types of PLM co-occurrences on the same lysine residues.Finally,various options were provided for accessing the data,while original references and other annotations were also present for each PLM substrate.Taken together,we anticipated the PLMD database can serve as a useful resource for further researches of PLMs.PLMD 3.0 was implemented in PHP ＋ MySQL and freely available at http：//plmd.biocuckoo.org.展开更多
Acylation has been shown to be an effective toolfor improving surface functional properties of plant proteins.Soy bean protein has been extensively modified throughchemical and enzvmatic treatments.Their effectiveness...Acylation has been shown to be an effective toolfor improving surface functional properties of plant proteins.Soy bean protein has been extensively modified throughchemical and enzvmatic treatments.Their effectiveness lies intheir high nutritional value and low cost,which promotetheir use as ingredients for the formulation of food products.This paper reports a complete review of chemical modificationof various proteins from plant and animal sources,The nutri-tive and toxicological aspects through in vitro and in vivotests are also described.展开更多
Herein,we report a semi-synthetic strategy affording a nitrophorin 2(NP2)variant with a N,N'-bis(2-pyridylmethyl)amine(Dpa)ligand as sidechain selectively installed at position 27,which was assembled from a synthe...Herein,we report a semi-synthetic strategy affording a nitrophorin 2(NP2)variant with a N,N'-bis(2-pyridylmethyl)amine(Dpa)ligand as sidechain selectively installed at position 27,which was assembled from a synthetic peptide thioester bearing the Dpa ligand and an expressed protein segment via native chemical ligation.The semi-synthetic NP2 was able to accept the natural heme b cofactor and the Dpa ligand was able to bind Cu(Ⅱ)/Fe(Ⅲ)ions,leading to heteronuclear active site.展开更多
Recent years have seen an ever increasing number of enzyme mediated protein/peptide modification reactions, which contribute significantly to the elucidation of related biological functions. The many available enzymes...Recent years have seen an ever increasing number of enzyme mediated protein/peptide modification reactions, which contribute significantly to the elucidation of related biological functions. The many available enzymes have, however, caused difficulties for practitioners in choosing the most appropriate enzyme for a certain purpose. This review surveyed the widely used enzymes(i.e., sortases, butelase 1,subtiligase, formylglycine generating enzyme and farnesyltransferase) in the manipulation of proteins/peptides, and the application fields of these enzymes as well as the advantages and limitations of each enzyme are summarized.展开更多
In the recent years,biological nanostructures coatings have been incorporated into orthopedic and dental implants in order to accelerate osseointegration and reducing surgical restrictions.In the present work,chemical...In the recent years,biological nanostructures coatings have been incorporated into orthopedic and dental implants in order to accelerate osseointegration and reducing surgical restrictions.In the present work,chemical etching,anodization and metal doping surface modification methods were integrated in one strategy to fabricate innovative titanium surfaces denominated by titanium nanoporous,anodized titanium nanoporous,silver-anodized titanium nanoporous and gold-anodized titanium nanoporous.The stability properties of nanostructures-coated surfaces were elucidated using electrochemical impedance spectroscopy（EIS） after 7 days of immersion in simulated biological fluids.Morphology and chemical compositions of new surfaces were characterized by scanning electron microscope and energy-dispersive X-ray analysis.The EIS results and data fitting to the electrical equivalent circuit model demonstrated the influence of adsorption of bovine serum albumin on new surfaces as a function of protein concentration.Adsorption process was described by the very well-known model of the Langmuir adsorption isotherm.The thermodynamic parameter DGADS（-50 to 59 kJ mol^（-1）） is calculated,which supports the instantaneous adsorption of protein from biological fluids to new surfaces and refers to their good biocompatibility.Ultimately,this study explores new surface strategy to gain new implants as a means of improving clinical outcomes of patients undergoing orthopedic surgery.展开更多
Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolit...Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolite regulates the protein functions, such as diacylglycerol to protein kinase C, lactose regulationof the lac repressor, and HIF-1α stabilization by 2-hydroxyglutarate. However, decades old traditionalbiochemical methods are insufficient to systematically investigate the bio-molecular reactions for a high-throughput discovery. Here, we have reviewed an update on the recently developed chemical proteomicscalled activity-based protein profiling （ABPP）. ABPP is able to identify proteins interacted eithercovalently or non-covalently with metabolites significantly. Thus, ABPP will facilitate the characteriza-tion of specific metabolite regulating; proteins in human disease progression.展开更多
Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,...Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,such as spinal cord injury with the embryonic stem cells(ESCs)-derived oligodendrocyte progenitor cells,and dry age-related macular degeneration(AMD)with the ESCs-derived retinal pigment epithelium,and have great application value in clinical regenerative medicine.展开更多
Stomatal closure,which serves to limit water loss,represents one of the most rapid and critical reactions of plants,occurring not only in response to drought but also to a range of other stressors,including salinity,e...Stomatal closure,which serves to limit water loss,represents one of the most rapid and critical reactions of plants,occurring not only in response to drought but also to a range of other stressors,including salinity,extreme temperatures,heavy metals,gaseous toxicants,and pathogen infection.ABA is considered to be the main regulator of stomatal movements in plants under abiotic stress.In the last two decades,however,the list of plant hormones and other physiologically active substances that affect stomatal status has expanded considerably.It is believed that stomata are regulated by a complex multicomponent network of compounds consisting of hormones and signaling mediators.A special place among them is occupied by gasotransmitters,endogenously synthesized gaseous compounds with signaling functions.The most studied of them are nitrogen monoxide(NO),hydrogen sulfide(H2S),and carbon monoxide(CO).Carbon dioxide(CO_(2)),not yet classified as a classical gasotransmitter,is also considered an important gaseous regulatory molecule.Information has been obtained on the ability of each of these gases to induce stomatal responses in plants.Gasotransmitters are also involved as mediators in stomatal responses induced by various plant hormones and other compounds,particularly ABA,jasmonic and salicylic acids,brassinosteroids,and polyamines.This review examines the functional interactions between gasotransmitters at the level of influencing each other’s synthesis and interactions with other mediators,especially ROS and calcium ions,in their involvement in providing stomatal responses.The latest information on proteins involved in stomatal regulation and undergoing post-translational modification under the action of gasotransmitters,including protein kinases,ion channel proteins,aquaporins,pro-and antioxidant enzymes,is also summarized.The possibilities of practical use of gasotransmitter donors as stress protective agents contributing to the normalization of plant water metabolism are considered.展开更多
基金supported by the National Natural Science Foundation of China(Nos.41975156,41675119)。
文摘Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.
文摘It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.
文摘Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.
基金This work was supported by the Zhenjiang Key Research and Development Plan(Social Development)(No.SH2019025)the Scientific Research Project of Health Commission of Jiangsu Province(No.Z2019036)+1 种基金the Science and Technology Innovation Fund Project of Zhenjiang City(No.SH2021066)the Taicang Science and Technology Planning Project(No.TC2020JCYL17),China.
文摘The onset of inflammatory bowel disease(IBD)involves many factors,including environmental parameters,microorganisms,and the immune system.Although research on IBD continues to expand,the specific pathogenesis mechanism is still unclear.Protein modification refers to chemical modification after protein biosynthesis,also known as post-translational modification(PTM),which causes changes in the properties and functions of proteins.Since proteins can be modified in different ways,such as acetylation,methylation,and phosphorylation,the functions of proteins in different modified states will also be different.Transitions between different states of protein or changes in modification sites can regulate protein properties and functions.Such modifications like neddylation,sumoylation,glycosylation,and acetylation can activate or inhibit various signaling pathways(e.g.,nuclear factor-κB(NF-κB),extracellular signal-regulated kinase(ERK),and protein kinase B(AKT))by changing the intestinal flora,regulating immune cells,modulating the release of cytokines such as interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interferon-γ(IFN-γ),and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier.In this review,we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.
基金financially supported by National Key Research and Development Program of China (No.2016YFA0201400)the National Natural Science Foundation of China (No.21778005)+1 种基金Peking University Health Science Center (Nos.BMU20160537 andBMU2017QQ006)the Youth Thousand-Talents Program of China for support
文摘Cysteine chemistry provides a low cost and convenient way for site-specific protein modification.However,recombinant expression of disulfide bonding containing protein with unpaired cysteine is technically challenging and the resulting protein often suffers from significantly reduced yield and activity.Here we used genetic code expansion technique to introduce a surface exposed self-paired dithiol functional group into proteins,which can be selectively reduced to afford active thiols.Two compounds containing self-paired disulfides were synthesized,and their genetic incorporations were validated using green fluorescent proteins(GFP).The compatibility of these self-paired di-thiols with natural disulfide bond was demonstrated using antibody fragment to afford site-specifically labeled antibody.This work provides another valuable building block into the chemical tool-box for site-specific labeling of proteins containing internal disulfides.
基金the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金the financial support from the General and Key Programs of the National Natural Science Foundation of China(32072288,32030086)Central Public-interest Scientific Institution Basal Research Fund(S2019RCJC01)。
文摘This study investigated the integrated atlas of protein phosphorylation,acetylation,ubiquitination and S-nitrosylation in pre-rigor(0.5 h)and post-rigor(5 days)lamb to interpret the roles of protein posttranslational modifications(PTMs)during meat aging.The results showed that the most common PTMs in postmortem meat were phosphorylated proteins.PTMs regulation during the postmortem period altered proteins involved in metabolic pathways and muscle contraction.The phosphorylation and ubiquitination of proteins located in mitochondria and nuclear changed significantly between 0.5 h and 5 days postmortem.Gene set enrichment analysis revealed possible roles of total PTMs proteins,with a general downregulation of phosphorylation,acetylation and ubiquitination.There was a weak correlation in the lysine PTM of acetylation and ubiquitination at the same site in postmortem meat.Multiple PTMs of proteins in glycolysis,TCA cycle,muscle contraction and the calcium signaling pathway cooperatively regulate meat quality development from pre-rigor to post-rigor.
基金supported by the National Natural Science Foundation of China(22174038,21925401,21904037,52221001)the Natural Science Foundation of Hunan Province(2022JJ20005,2020JJ4173)。
文摘Signal pathways participate in vital biological processes and regulate complex life activities through protein modifications.Protein modifications in signal pathways are accompanied by electron transfer.The study of electronic behavior helps to explore the physical and chemical processes in signal pathways,receiving extensive attention.There are some excellent reviews that have summarized methods for signal pathway detection,while few discussions are from an electron transfer perspective.This review describes the relationship between signal pathways and electron transfer in protein modification.Subsequently,we summarize the electron transfer-based detection methods,such as electrochemical,photoelectrochemical and electrochemiluminescence methods.Additionally,the applications of signal pathway detection in mechanism study and imaging are also reviewed.Finally,a comprehensive discussion of the summary and outlooks in this field is presented,aiming to provide valuable guidance for the molecular mechanism of life processes and the development of new analytical techniques.
基金supported by the National Key R&D Program of China(Grant No.2020YFA0907800)the National Natural Science Foundation of China(Grant Nos.32170043 and 82173720).
文摘Streptomycetes possess numerous gene clusters and the potential to produce a large amount of natural products.Histone deacetylase(HDAC)inhibitors play an important role in the regulation of histone modifications in fungi,but their roles in prokaryotes remain poorly understood.Here,we investigated the global effects of the HDAC inhibitor,sodium butyrate(SB),on marine-derived Streptomyces olivaceus FXJ 8.021,particularly focusing on the activation of secondary metabolite biosynthesis.The antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters(BGCs)in strain FXJ 8.021,among which the silent lobophorin BGC was activated by SB.Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis(ge00097–ge00139)and CoA-ester formation(e.g.,ge02824),as well as the glycolysis/gluconeogenesis pathway(e.g.,ge01661),was significantly up-regulated in the presence of SB.Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester,thereby increasing the precursor supply for lobophorin biosynthesis.Further acetylomic analysis revealed that the acetylation levels on 218 sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated.These acetylated proteins were particularly enriched in transcriptional and translational machinery components(e.g.,elongation factor GE04399),and their correlations with the proteins involved in lobophorin biosynthesis were established by protein–protein interaction network analysis,suggesting that SB might function via a complex hierarchical.
文摘Timely removal of oxidatively damaged proteins is crit- ical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modifi- cation that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 （deleted in split hand/split foot 1）, an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSSl-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin- proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as amodifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.
基金supported by Shandong Provincial Natural Science Foundation,China(No.ZR2020QC081,H.Jiang)Youth Innovation Team Talent Introduction Program of Shandong Province(No.20190164,R.Zhang and H.Jiang)。
文摘Numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological chemistry.Approaches for site-specific modification of native amino acid residues in test tubes and biological contexts represent novel biological tools for understanding the role of peptides and proteins.Selective N-terminal modification strategies have been broadly studied especially in the last 10 years,as N-terminal positions are typically solvent exposed and provide chemically distinct sites for many peptide and protein targets,making N terminus distinct from other functional groups.A growing number of chemical and enzymatic techniques have been developed to modify N-terminal amino acids,and those techniques have the potential in the fields of medicine,basic research and applied materials science.This review focuses on appraising modification methodologies with the potential for biological applications from the past 10 years.
基金supported by grants from the National Basic Research Program(973 projectNo.2013CB933900)+1 种基金the Natural Science Foundation of China(Nos.31671360 andJ1103514)the International Science & Technology Cooperation Program of China (No.2014DFB30020)
文摘Post-translational modifications（PTMs） occurring at protein lysine residues,or protein lysine modifications（PLMs）,play critical roles in regulating biological processes.Due to the explosive expansion of the amount of PLM substrates and the discovery of novel PLM types,here we greatly updated our previous studies,and presented a much more integrative resource of protein lysine modification database（PLMD）.In PLMD,we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs,including ubiquitination, acetylation, sumoylation, methylation ,succinylation,malonylation,glutarylation,giycation,formylation,hydroxylation,butyrylation,propionylation,crotonylation,pupylation,neddylation,2-hydroxyisobutyrylation,phosphoglycerylation,carboxylation,lipoylation and biotinylation.Using the data set,a motif-based analysis was performed for each PLM type,and the results demonstrated that different PLM types preferentially recognize distinct sequence motifs for the modifications.Moreover,various PLMs synergistically orchestrate specific cellular biological processes by mutual crosstalks with each other,and we totally found 65,297 PLM events involved in 90 types of PLM co-occurrences on the same lysine residues.Finally,various options were provided for accessing the data,while original references and other annotations were also present for each PLM substrate.Taken together,we anticipated the PLMD database can serve as a useful resource for further researches of PLMs.PLMD 3.0 was implemented in PHP ＋ MySQL and freely available at http：//plmd.biocuckoo.org.
文摘Acylation has been shown to be an effective toolfor improving surface functional properties of plant proteins.Soy bean protein has been extensively modified throughchemical and enzvmatic treatments.Their effectiveness lies intheir high nutritional value and low cost,which promotetheir use as ingredients for the formulation of food products.This paper reports a complete review of chemical modificationof various proteins from plant and animal sources,The nutri-tive and toxicological aspects through in vitro and in vivotests are also described.
基金financial support from the National Natural Science Foundation of China(Nos.22077036 and 22277029)is greatly acknowledged.
文摘Herein,we report a semi-synthetic strategy affording a nitrophorin 2(NP2)variant with a N,N'-bis(2-pyridylmethyl)amine(Dpa)ligand as sidechain selectively installed at position 27,which was assembled from a synthetic peptide thioester bearing the Dpa ligand and an expressed protein segment via native chemical ligation.The semi-synthetic NP2 was able to accept the natural heme b cofactor and the Dpa ligand was able to bind Cu(Ⅱ)/Fe(Ⅲ)ions,leading to heteronuclear active site.
基金The financial support from the National Recruitment Program of Global Youth Experts(1000 Talents Plan)the National Natural Science Foundation of China (No. 81703406)
文摘Recent years have seen an ever increasing number of enzyme mediated protein/peptide modification reactions, which contribute significantly to the elucidation of related biological functions. The many available enzymes have, however, caused difficulties for practitioners in choosing the most appropriate enzyme for a certain purpose. This review surveyed the widely used enzymes(i.e., sortases, butelase 1,subtiligase, formylglycine generating enzyme and farnesyltransferase) in the manipulation of proteins/peptides, and the application fields of these enzymes as well as the advantages and limitations of each enzyme are summarized.
文摘In the recent years,biological nanostructures coatings have been incorporated into orthopedic and dental implants in order to accelerate osseointegration and reducing surgical restrictions.In the present work,chemical etching,anodization and metal doping surface modification methods were integrated in one strategy to fabricate innovative titanium surfaces denominated by titanium nanoporous,anodized titanium nanoporous,silver-anodized titanium nanoporous and gold-anodized titanium nanoporous.The stability properties of nanostructures-coated surfaces were elucidated using electrochemical impedance spectroscopy（EIS） after 7 days of immersion in simulated biological fluids.Morphology and chemical compositions of new surfaces were characterized by scanning electron microscope and energy-dispersive X-ray analysis.The EIS results and data fitting to the electrical equivalent circuit model demonstrated the influence of adsorption of bovine serum albumin on new surfaces as a function of protein concentration.Adsorption process was described by the very well-known model of the Langmuir adsorption isotherm.The thermodynamic parameter DGADS（-50 to 59 kJ mol^（-1）） is calculated,which supports the instantaneous adsorption of protein from biological fluids to new surfaces and refers to their good biocompatibility.Ultimately,this study explores new surface strategy to gain new implants as a means of improving clinical outcomes of patients undergoing orthopedic surgery.
基金supported by the National Natural Science Foundation of China(No.81672440)Innovation Program of Science and Research from the DICP,CAS(No.DICP TMSR201601)the 100 Talents Program of Chinese Academy of Sciences
文摘Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolite regulates the protein functions, such as diacylglycerol to protein kinase C, lactose regulationof the lac repressor, and HIF-1α stabilization by 2-hydroxyglutarate. However, decades old traditionalbiochemical methods are insufficient to systematically investigate the bio-molecular reactions for a high-throughput discovery. Here, we have reviewed an update on the recently developed chemical proteomicscalled activity-based protein profiling （ABPP）. ABPP is able to identify proteins interacted eithercovalently or non-covalently with metabolites significantly. Thus, ABPP will facilitate the characteriza-tion of specific metabolite regulating; proteins in human disease progression.
基金supported by the National Key Research and Development Program of China(2024YFA0916400)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000)+5 种基金the National Natural Science Foundation of China(32025010,32488301,92254301,92357302,92157202,32241002,32261160376,32322022,and 32471358)Major Project of Guangzhou National Laboratory(GZNL2024A03006 and GZNL2024B01003)the Key Research Program,CAS(ZDBS-ZRKJZ-TLC003,YSBR-075 and 188GJHZ2024048GC)Guangdong Province Science and Technology Program(2023B0303000023,2023B1111050005,2023B1212060050,2023B1212120009,2024B1515040020,and 2024A1515010782)Guangzhou Science and Technology Program(202206060002 and 2025A04J7110)Health@InnoHK funding support from the Innovation Technology Commission of the Hong Kong SAR,and Major Research Project(GIBHMRP25-01)Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences.
文摘Pluripotent stem cells(PSCs)possess the ability to proliferate indefinitely,self-renew,and differentiate into three germ layers.These pluripotent characteristics allow PSCs to be used to treat many incurable diseases,such as spinal cord injury with the embryonic stem cells(ESCs)-derived oligodendrocyte progenitor cells,and dry age-related macular degeneration(AMD)with the ESCs-derived retinal pigment epithelium,and have great application value in clinical regenerative medicine.
基金supported by Projects 14.00.02.06.P“Development of Methods of Seed Priming of Cereal Grains by the Action of Donors of Gasotransmitters and Compounds with Hormonal Activity”(state registration number of work 0124U000126)III-2-23“Genetic and Epigenetic Mechanisms and Factors of Protective and Adaptive Reactions of Plants”(state registration number of work 0123U101054).
文摘Stomatal closure,which serves to limit water loss,represents one of the most rapid and critical reactions of plants,occurring not only in response to drought but also to a range of other stressors,including salinity,extreme temperatures,heavy metals,gaseous toxicants,and pathogen infection.ABA is considered to be the main regulator of stomatal movements in plants under abiotic stress.In the last two decades,however,the list of plant hormones and other physiologically active substances that affect stomatal status has expanded considerably.It is believed that stomata are regulated by a complex multicomponent network of compounds consisting of hormones and signaling mediators.A special place among them is occupied by gasotransmitters,endogenously synthesized gaseous compounds with signaling functions.The most studied of them are nitrogen monoxide(NO),hydrogen sulfide(H2S),and carbon monoxide(CO).Carbon dioxide(CO_(2)),not yet classified as a classical gasotransmitter,is also considered an important gaseous regulatory molecule.Information has been obtained on the ability of each of these gases to induce stomatal responses in plants.Gasotransmitters are also involved as mediators in stomatal responses induced by various plant hormones and other compounds,particularly ABA,jasmonic and salicylic acids,brassinosteroids,and polyamines.This review examines the functional interactions between gasotransmitters at the level of influencing each other’s synthesis and interactions with other mediators,especially ROS and calcium ions,in their involvement in providing stomatal responses.The latest information on proteins involved in stomatal regulation and undergoing post-translational modification under the action of gasotransmitters,including protein kinases,ion channel proteins,aquaporins,pro-and antioxidant enzymes,is also summarized.The possibilities of practical use of gasotransmitter donors as stress protective agents contributing to the normalization of plant water metabolism are considered.
