Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans.One example is SARS,which caused a worldwide health threat in 2003.In coronaviruses,the structural protein N(nucleocapsid...Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans.One example is SARS,which caused a worldwide health threat in 2003.In coronaviruses,the structural protein N(nucleocapsid protein)associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription.The structure of Nterminal domain of MHV N protein also implicated its specific affinity with transcriptional regulatory sequence(TRS)RNA.Here we report the crystal structures of the two proteolytically resistant N-(NTD)and C-terminal(CTD)domains of the N protein from murine hepatitis virus(MHV).The structure of NTD in two different crystal forms was solved to 1.5Å.The higher resolution provides more detailed structural information than previous reports,showing that the NTD structure from MHV shares a similar overall and topology structure with that of SARS-CoV and IBV,but varies in its potential surface,which indicates a possible difference in RNA-binding module.The structure of CTD was solved to 2.0-Åresolution and revealed a tightly intertwined dimer.This is consistent with analytical ultracentrifugation experiments,suggesting a dimeric assembly of the N protein.The similarity between the structures of these two domains from SARS-CoV,IBV and MHV corroborates a conserved mechanism of nucleocapsid formation for coronaviruses.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.30730022)the National Basic Research Program(973 Program)(Grant No.2006CB806503)+2 种基金the National Programs for High Technology Research and Development Program(863 Program)(Grant Nos.2006AA02A322 and 2006AA020502)the National Major Project(Grant No.2009ZX10004-304)the Chinese Academy of Sciences Grant KSCX2-YW-R-05 to Z.R.
文摘Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans.One example is SARS,which caused a worldwide health threat in 2003.In coronaviruses,the structural protein N(nucleocapsid protein)associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription.The structure of Nterminal domain of MHV N protein also implicated its specific affinity with transcriptional regulatory sequence(TRS)RNA.Here we report the crystal structures of the two proteolytically resistant N-(NTD)and C-terminal(CTD)domains of the N protein from murine hepatitis virus(MHV).The structure of NTD in two different crystal forms was solved to 1.5Å.The higher resolution provides more detailed structural information than previous reports,showing that the NTD structure from MHV shares a similar overall and topology structure with that of SARS-CoV and IBV,but varies in its potential surface,which indicates a possible difference in RNA-binding module.The structure of CTD was solved to 2.0-Åresolution and revealed a tightly intertwined dimer.This is consistent with analytical ultracentrifugation experiments,suggesting a dimeric assembly of the N protein.The similarity between the structures of these two domains from SARS-CoV,IBV and MHV corroborates a conserved mechanism of nucleocapsid formation for coronaviruses.
