The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains a...The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.展开更多
基金supported by grants of the National Basic Research Priorities Program of China (2015CB554304)
文摘The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(HCV)assembly.In this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in HCV assembly.Multiple regions of PLA1A were involved in their interaction and complex formation.Furthermore,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in cells.Meanwhile,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain 1.Interestingly,these amino acids in the sequence are also essential for viral RNA replication.Further experiments revealed that these four proteins interact with each other.Moreover,PLA1A expression levels were elevated in livers from HCV-infected patients.In conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for HCV assembly and provided a detailed characterization of PLA1A in HCV assembly.
