Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases(NMTs),which are ubiquitous enzymes in eukaryotes.Specifically,attachment of a myristoyl group is vital for proteins partici...Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases(NMTs),which are ubiquitous enzymes in eukaryotes.Specifically,attachment of a myristoyl group is vital for proteins participating in various biological functions,including signal transduction,cellular localization,and oncogenesis.Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections.In this review,we describe the current understanding of protein N-myristoylation(mainly focusing on myristoyl switches)and summarize its crucial roles in regulating innate immune responses,including TLR4-dependent inflammatory responses and demyristoylation-induced innate immunosuppression during Shigella flexneri infection.Furthermore,we examine the role of myristoylation in viral assembly,intracellular host interactions,and viral spread during human immunodeficiency virus-1(HIV-1)infection.Deeper insight into the relationship between protein N-myristoylation and innate immunity might enable us to clarify the pathogenesis of certain infectious diseases and better harness protein N-myristoylation for new therapeutics.展开更多
Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is ...Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is highly conserved from Caenorhabditis elegans to mammals,the domain structure,subcellular localization,and exact function of HID-1 remain unknown.Previous studies and various bioinformatic softwares predicted that HID-1 contained many transmembrane domains but no known functional domain.In this study,we revealed that mammalian HID-1 localized to the medial-and transGolgi apparatus as well as the cytosol,and the localization was sensitive to brefeldin A treatment.Next,we demonstrated that HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol.Finally,we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus.We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region.展开更多
基金supported by a special program from the Ministry o f Science and Technology of China(2016YFA0502500 to L.Z.)the Chinese National Natural Science Funds(U20A20393,82041009,31925013,31671457,and 91753139 to LZ.,31871405 and 31571460 to FZ.)+3 种基金Jiangsu National Science Foundation(BK20180043 and 19KJA550003 to F.Z.)the Zhejiang Natural Science Fund(LD19C070001 to L.Z.)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases(NMTs),which are ubiquitous enzymes in eukaryotes.Specifically,attachment of a myristoyl group is vital for proteins participating in various biological functions,including signal transduction,cellular localization,and oncogenesis.Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections.In this review,we describe the current understanding of protein N-myristoylation(mainly focusing on myristoyl switches)and summarize its crucial roles in regulating innate immune responses,including TLR4-dependent inflammatory responses and demyristoylation-induced innate immunosuppression during Shigella flexneri infection.Furthermore,we examine the role of myristoylation in viral assembly,intracellular host interactions,and viral spread during human immunodeficiency virus-1(HIV-1)infection.Deeper insight into the relationship between protein N-myristoylation and innate immunity might enable us to clarify the pathogenesis of certain infectious diseases and better harness protein N-myristoylation for new therapeutics.
基金the National Science Foundation of China(Grant Nos.30870564,and 30900268),The Beijing Natural Science Foundation(No.5092017)the Major State Basic Research Program of China(No.2010CB833701)the CAS Project(KSCX2-SW-224 and Novo Nordisk-CAS to P Xu).
文摘Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is highly conserved from Caenorhabditis elegans to mammals,the domain structure,subcellular localization,and exact function of HID-1 remain unknown.Previous studies and various bioinformatic softwares predicted that HID-1 contained many transmembrane domains but no known functional domain.In this study,we revealed that mammalian HID-1 localized to the medial-and transGolgi apparatus as well as the cytosol,and the localization was sensitive to brefeldin A treatment.Next,we demonstrated that HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol.Finally,we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus.We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region.
