title: Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM.
abstract: 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 9.1 Å resolution 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) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified 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 floor 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 attaching unique functional tegument proteins outside.
authors.affiliation: The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
authors.forename: Wong H
authors.initials: WH
authors.lastname: Hui
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Tang
authors.forename: Hongrong
authors.initials: H
authors.lastname: Liu
authors.forename: Ivo
authors.initials: I
authors.lastname: Atanasov
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000737:chemistry / Q000648:ultrastructure*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D036022:Capsid Proteins