Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but mole...Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described.Here,we report a cryo electron microscopy(cryoEM)structure of the murine cytomegalovirus(MCMV)capsid at a 9.1Åresolution and describe the molecular interactions among the~3000 protein molecules in the MCMV capsid at the secondary structure level.Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling.The major capsid protein(MCP)upper domain(MCPud)containsα-helices andβ-sheets conserved with those in MCPud of herpes simplex virus type 1(HSV-1),with the largest differences identifi ed as a“saddle loop”region,located at the tip of MCPud and involved in interaction with the smallest capsid protein(SCP).Interactions among the bacteriophage HK97-like fl oor domain of MCP,the middle domain of MCP,the hook and clamp domains of the triplex proteins(hoop and clamp domains of TRI-1 and clamp domain of TRI-2)contribute to the formation of a mature capsid.These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attach-ing unique functional tegument proteins outside.展开更多
基金the cryoEM facility in the Electron Imaging Center for Nanomachines by NIH(1S10RR23057 to ZHZ)and CNSI at UCLA.
文摘Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described.Here,we report a cryo electron microscopy(cryoEM)structure of the murine cytomegalovirus(MCMV)capsid at a 9.1Åresolution and describe the molecular interactions among the~3000 protein molecules in the MCMV capsid at the secondary structure level.Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling.The major capsid protein(MCP)upper domain(MCPud)containsα-helices andβ-sheets conserved with those in MCPud of herpes simplex virus type 1(HSV-1),with the largest differences identifi ed as a“saddle loop”region,located at the tip of MCPud and involved in interaction with the smallest capsid protein(SCP).Interactions among the bacteriophage HK97-like fl oor domain of MCP,the middle domain of MCP,the hook and clamp domains of the triplex proteins(hoop and clamp domains of TRI-1 and clamp domain of TRI-2)contribute to the formation of a mature capsid.These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attach-ing unique functional tegument proteins outside.
