In plant chloroplasts,photosystem II(PSII)complexes,together with light-harvesting complex II(LHCII),form various PSII-LHCII supercomplexes(SCs).This process likely involves immunophilins,but the underlying regulatory...In plant chloroplasts,photosystem II(PSII)complexes,together with light-harvesting complex II(LHCII),form various PSII-LHCII supercomplexes(SCs).This process likely involves immunophilins,but the underlying regulatory mechanisms are unclear.Here,by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen-localized immunophilin CYCLOPHILIN28(CYP28)to wildtype and transgenic complemented lines,we determined that CYP28 regulates the assembly and accumulation of PSII-LHCII SCs.Compared to the wild type,cyp28 plants showed accelerated leaf growth,earlier flowering time,and enhanced accumulation of high molecular weight PSII-LHCII SCs under normal light conditions.The lack of CYP28 also significantly affected the electron transport rate.Blue native-polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M-LHCII-Lhcb4-Lhcb6 complexes in cyp28 versus wild-type plants.Peptidyl-prolyl cis/trans isomerase(PPIase)activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity.Mutant analysis suggested that CYP28 may regulate PSIILHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity.Furthermore,the Lhcb6-P139 residue is critical for PSII-LHCII SC assembly and accumulation.Therefore,our findings suggest that CYP28 likely regulates PSII-LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.展开更多
Cotton fiber is a highly elongated and thickened single cell that produces large quantities of cellulose,which is synthesized and assembled into cell wall microfibrils by the cellulose synthase complex(CSC).In this st...Cotton fiber is a highly elongated and thickened single cell that produces large quantities of cellulose,which is synthesized and assembled into cell wall microfibrils by the cellulose synthase complex(CSC).In this study,we report that in cotton(Gossypium hirsutum)fibers harvested during secondary cell wall(SCW)synthesis,GhCesA 4,7,and 8 assembled into heteromers in a previously uncharacterized 36-mer-like cellulose synthase supercomplex(CSS).This super CSC was observed in samples prepared using cotton fiber cells harvested during the SCW synthesis period but not from cotton stem tissue or any samples obtained from Arabidopsis.Knock-out of any of GhCesA 4,7,and 8 resulted in the disappearance of the CSS and the production of fiber cells with no SCW thickening.Cotton fiber CSS showed significantly higher enzyme activity than samples prepared from knock-out cotton lines.We found that the microfibrils from the SCW of wild-type cotton fibers may contain 72 glucan chains in a bundle,unlike other plant materials studied.GhCesA4,7,and 8 restored both the dwarf and reduced vascular bundle phenotypes of their orthologous Arabidopsis mutants,potentially by reforming the CSC hexamers.Genetic complementation was not observed when non-orthologous CesA genes were used,indicating that each of the three subunits is indispensable for CSC formation and for full cellulose synthase function.Characterization of cotton CSS will increase our understanding of the regulation of SCW biosynthesis.展开更多
The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation.The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane ...The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation.The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane has been replaced by the solid state supercomplex model wherein the respiratory complexes associate with each other to form supramolecular complexes.Defects in these supercomplexes,which have been shown to be functionally active and required for forming stable respiratory complexes,have been associated with many genetic and neurodegenerative disorders demonstrating their biomedical signifi cance.In this review,we will summarize the functional and structural signifi cance of supercomplexes and provide a comprehensive review of their assembly and the assembly factors currently known to play a role in this process.展开更多
Funded by the National Natural Science Foundation of China(NSFC),Ministry of Science and Technology of China,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chines...Funded by the National Natural Science Foundation of China(NSFC),Ministry of Science and Technology of China,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chinese Academy of Sciences,led by Dr.Liu Zhenfeng(柳振峰),Dr.Zhang Xinzheng(章新政)and Dr.Li Mei(李梅)respectively,solved the structure of spinach photosystem II-LHCII supercom-展开更多
Funded by the National Natural Science Foundation of China,Chinese Ministry of Science and Technology,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chinese Acade...Funded by the National Natural Science Foundation of China,Chinese Ministry of Science and Technology,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chinese Academy of Sciences,namely Liu Zhenfeng’s(柳振峰),Zhang展开更多
Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disrupti...Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein-protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using ＂Mirror tree＂ method on the respiratory chain （RC） proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions （Wilcoxon test, p-value = 4.4 × 10 6）. Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein-protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study.展开更多
The Clifford algebra is a unification and generalization of real number, complex number, quaternion, and vector algebra, which accurately and faithfully characterizes the intrinsic properties of space-time, providing ...The Clifford algebra is a unification and generalization of real number, complex number, quaternion, and vector algebra, which accurately and faithfully characterizes the intrinsic properties of space-time, providing a unified, standard, elegant, and open language and tools for numerous complicated mathematical and physical theories. So it is worth popularizing in the teaching of undergraduate physics and mathematics. Clifford algebras can be directly generalized to 2<sup>n</sup>-ary associative algebras. In this generalization, the matrix representation of the orthonormal basis of space-time plays an important role. The matrix representation carries more information than the abstract definition, such as determinant and the definition of inverse elements. Without this matrix representation, the discussion of hypercomplex numbers will be difficult. The zero norm set of hypercomplex numbers is a closed set of special geometric meanings, like the light-cone in the realistic space-time, which has no substantial effect on the algebraic calculus. The physical equations expressed in Clifford algebra have a simple formalism, symmetrical structure, standard derivation, complete content. Therefore, we can hope that this magical algebra can complete a new large synthesis of modern science.展开更多
After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organiz...After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organize homogeneous divisions of the limited development of the exponential function, that is opening the way to the use of a whole bunch of new primary functions in Differential Calculus. He then shows how new supercomplex products in dimension 3 make it possible to calculate fractals whose connexity depends on the product considered. We recall the geometry of convex polygons and regular polygons.展开更多
Sorafenib,a multi-kinase inhibitor for advanced hepatocellular carcinoma(HCC),often encounters resistance within months of treatment,limiting its long-term efficacy.Despite extensive efforts,reliable plasma biomarkers...Sorafenib,a multi-kinase inhibitor for advanced hepatocellular carcinoma(HCC),often encounters resistance within months of treatment,limiting its long-term efficacy.Despite extensive efforts,reliable plasma biomarkers to monitor drug activity remain elusive.Here,we demonstrate that metabolic reprogramming is a strategic response implemented by cancer cells to survive the therapeutic pressure.Sorafenib suppresses oxidative phosphorylation by disrupting electron transport chain supercomplex assembly and enhancing glycolysis.To mitigate the accumulation of harmful glycolytic byproducts such as advanced glycation endproducts(AGEs),sorafenib-treated cells reroute excess dihydroxyacetone phosphate(DHAP)toward glycerol-3-phosphate(G3P)synthesis,supporting glycerolipid metabolism,NAD^(+)regeneration,and redox balance,rather than producing D-lactate via the glyoxalase pathway.Alongside,resistant cells enhance serine metabolism to boost glutathione synthesis,reinforcing antioxidant defenses.Additionally,sorafenib increases reliance on exogenous non-esterified free fatty acids and triglycerides for phospholipid remodeling.The combined effects of glycerolipid remodeling and enhanced antioxidant capacity facilitate ferroptosis escape,diminishing sorafenib’s activity.Leveraging these metabolic insights,we validate our findings by investigating plasma metabolites alteration in HCC patients.We identify D-lactate accumulation as a predictor of treatment response and glycerol accumulation as a marker of resistance,highlighting their potential as novel biomarkers for sorafenib activity.As sorafenib is used in advanced HCC,early detection of treatment response is critical to guiding the therapeutic decision,optimizing treatment strategies,and improving patient outcomes.展开更多
基金supported by the National Natural Science Foundation of China(31700206)the Natural Science Basic Research Program of Shaanxi(2016JM3023)the Special Scientific Research Project of Education Department of Shaanxi Province(16JK1792)。
文摘In plant chloroplasts,photosystem II(PSII)complexes,together with light-harvesting complex II(LHCII),form various PSII-LHCII supercomplexes(SCs).This process likely involves immunophilins,but the underlying regulatory mechanisms are unclear.Here,by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen-localized immunophilin CYCLOPHILIN28(CYP28)to wildtype and transgenic complemented lines,we determined that CYP28 regulates the assembly and accumulation of PSII-LHCII SCs.Compared to the wild type,cyp28 plants showed accelerated leaf growth,earlier flowering time,and enhanced accumulation of high molecular weight PSII-LHCII SCs under normal light conditions.The lack of CYP28 also significantly affected the electron transport rate.Blue native-polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M-LHCII-Lhcb4-Lhcb6 complexes in cyp28 versus wild-type plants.Peptidyl-prolyl cis/trans isomerase(PPIase)activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity.Mutant analysis suggested that CYP28 may regulate PSIILHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity.Furthermore,the Lhcb6-P139 residue is critical for PSII-LHCII SC assembly and accumulation.Therefore,our findings suggest that CYP28 likely regulates PSII-LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.
基金This work was supported by the National Natural Science Foundation of China(31690090,31690091,31830057,32070207)the Foundation of Hubei Hongshan Laboratory(2021hszd014).
文摘Cotton fiber is a highly elongated and thickened single cell that produces large quantities of cellulose,which is synthesized and assembled into cell wall microfibrils by the cellulose synthase complex(CSC).In this study,we report that in cotton(Gossypium hirsutum)fibers harvested during secondary cell wall(SCW)synthesis,GhCesA 4,7,and 8 assembled into heteromers in a previously uncharacterized 36-mer-like cellulose synthase supercomplex(CSS).This super CSC was observed in samples prepared using cotton fiber cells harvested during the SCW synthesis period but not from cotton stem tissue or any samples obtained from Arabidopsis.Knock-out of any of GhCesA 4,7,and 8 resulted in the disappearance of the CSS and the production of fiber cells with no SCW thickening.Cotton fiber CSS showed significantly higher enzyme activity than samples prepared from knock-out cotton lines.We found that the microfibrils from the SCW of wild-type cotton fibers may contain 72 glucan chains in a bundle,unlike other plant materials studied.GhCesA4,7,and 8 restored both the dwarf and reduced vascular bundle phenotypes of their orthologous Arabidopsis mutants,potentially by reforming the CSC hexamers.Genetic complementation was not observed when non-orthologous CesA genes were used,indicating that each of the three subunits is indispensable for CSC formation and for full cellulose synthase function.Characterization of cotton CSS will increase our understanding of the regulation of SCW biosynthesis.
基金The relevant work carried out in the authors’laboratory has been supported by grants from National Institute of Health(R21 NS072777)the Morrison Trust.
文摘The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation.The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane has been replaced by the solid state supercomplex model wherein the respiratory complexes associate with each other to form supramolecular complexes.Defects in these supercomplexes,which have been shown to be functionally active and required for forming stable respiratory complexes,have been associated with many genetic and neurodegenerative disorders demonstrating their biomedical signifi cance.In this review,we will summarize the functional and structural signifi cance of supercomplexes and provide a comprehensive review of their assembly and the assembly factors currently known to play a role in this process.
文摘Funded by the National Natural Science Foundation of China(NSFC),Ministry of Science and Technology of China,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chinese Academy of Sciences,led by Dr.Liu Zhenfeng(柳振峰),Dr.Zhang Xinzheng(章新政)and Dr.Li Mei(李梅)respectively,solved the structure of spinach photosystem II-LHCII supercom-
文摘Funded by the National Natural Science Foundation of China,Chinese Ministry of Science and Technology,and Chinese Academy of Sciences,ajoint team of three laboratories from the Institute of Biophysics of Chinese Academy of Sciences,namely Liu Zhenfeng’s(柳振峰),Zhang
基金supported by the grants from the National Science Foundation of China(No.31071163)the National Basic Research Program(973 Program)(No.2010CB126604)the Ministry of Science and Technology of the People's Republic of China
文摘Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein-protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using ＂Mirror tree＂ method on the respiratory chain （RC） proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions （Wilcoxon test, p-value = 4.4 × 10 6）. Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein-protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study.
文摘The Clifford algebra is a unification and generalization of real number, complex number, quaternion, and vector algebra, which accurately and faithfully characterizes the intrinsic properties of space-time, providing a unified, standard, elegant, and open language and tools for numerous complicated mathematical and physical theories. So it is worth popularizing in the teaching of undergraduate physics and mathematics. Clifford algebras can be directly generalized to 2<sup>n</sup>-ary associative algebras. In this generalization, the matrix representation of the orthonormal basis of space-time plays an important role. The matrix representation carries more information than the abstract definition, such as determinant and the definition of inverse elements. Without this matrix representation, the discussion of hypercomplex numbers will be difficult. The zero norm set of hypercomplex numbers is a closed set of special geometric meanings, like the light-cone in the realistic space-time, which has no substantial effect on the algebraic calculus. The physical equations expressed in Clifford algebra have a simple formalism, symmetrical structure, standard derivation, complete content. Therefore, we can hope that this magical algebra can complete a new large synthesis of modern science.
文摘After having laid down the Axiom of Algebra, bringing the creation of the square root of -1 by Euler to the entire circle and thus authorizing a simple notation of the nth roots of unity, the author uses it to organize homogeneous divisions of the limited development of the exponential function, that is opening the way to the use of a whole bunch of new primary functions in Differential Calculus. He then shows how new supercomplex products in dimension 3 make it possible to calculate fractals whose connexity depends on the product considered. We recall the geometry of convex polygons and regular polygons.
基金Research from the corresponding author's laboratory was supported by grants from the National Natural Science Foundation of China(No.31771320,31571224,31110103919).
基金supported by the Ministry of University and Research(MUR)Progetto Eccellenza(2023-2027)to the Department of Pharmacological and Biomolecular Sciences“Rodolfo Paoletti,”Universita degli Studi di Milano,and partially by the Italian Ministry of Health with Ricerca Corrente and“5xmille”funds to N.Msupported by Fondazione Umberto Veronesi post-doctoral fellowship+5 种基金supported by a European Commission Horizon Europe Marie Skłodowska-Curie Actions Doctoral Networks(MSCA-DN)ETERNITY project(grant agreement number:101072759)coordinated by N.Msupported by Progetti di Rilevante Interesse Nazionale(PRIN 20227KTSAT to GDN)PNRR Missione 4(Progetto CN3-National Center for Gene Therapy and Drugs based on RNA Technology to GDN)PNRR Missione 4(Progetto MUSA-Multilayered Urban Sustainability Action to GDN)PNRR Missione 6(PNRR-MAD-2022-12375913 to GDN)CARDINNOV,Ministry of Research and University under the umbrella of the Partnership Fostering a European Research Area for Health(ERA4Health)(grant agreement number:101095426 of the EU Horizon Europe Research and Innovation Programme to GDN),European Atherosclerosis Society(EAS)Research grant 2023 to LDD.
文摘Sorafenib,a multi-kinase inhibitor for advanced hepatocellular carcinoma(HCC),often encounters resistance within months of treatment,limiting its long-term efficacy.Despite extensive efforts,reliable plasma biomarkers to monitor drug activity remain elusive.Here,we demonstrate that metabolic reprogramming is a strategic response implemented by cancer cells to survive the therapeutic pressure.Sorafenib suppresses oxidative phosphorylation by disrupting electron transport chain supercomplex assembly and enhancing glycolysis.To mitigate the accumulation of harmful glycolytic byproducts such as advanced glycation endproducts(AGEs),sorafenib-treated cells reroute excess dihydroxyacetone phosphate(DHAP)toward glycerol-3-phosphate(G3P)synthesis,supporting glycerolipid metabolism,NAD^(+)regeneration,and redox balance,rather than producing D-lactate via the glyoxalase pathway.Alongside,resistant cells enhance serine metabolism to boost glutathione synthesis,reinforcing antioxidant defenses.Additionally,sorafenib increases reliance on exogenous non-esterified free fatty acids and triglycerides for phospholipid remodeling.The combined effects of glycerolipid remodeling and enhanced antioxidant capacity facilitate ferroptosis escape,diminishing sorafenib’s activity.Leveraging these metabolic insights,we validate our findings by investigating plasma metabolites alteration in HCC patients.We identify D-lactate accumulation as a predictor of treatment response and glycerol accumulation as a marker of resistance,highlighting their potential as novel biomarkers for sorafenib activity.As sorafenib is used in advanced HCC,early detection of treatment response is critical to guiding the therapeutic decision,optimizing treatment strategies,and improving patient outcomes.
