RESEARCH ARTICLE

Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

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  • 1. The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; 2. Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA; 3. Department of Microbiology/AIDS program, Ponce School of Medicine, 395 Zona Industrial, Reparadara-2, Ponce, PR 00716, USA; 4. School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA; 5. Department of Microbiology and Molecular Genetics, International Center for Public Health (or ICPH), Room E350D, 225 Warren Street, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA; 6. Current address: College of Physics and Information Science, Hunan Normal University, Changsha 410081, China

Received date: 15 Jul 2013

Accepted date: 14 Aug 2013

Published date: 01 Nov 2013

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 ? resolution and describe the molecular interactions among the ~3000 protein molecules in the CMV 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.

Cite this article

Wong H. Hui, Qiyi Tang, Hongrong Liu, Ivo Atanasov, Fenyong Liu, Hua Zhu, Z. Hong Zhou . Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM[J]. Protein & Cell, 2013 , 4(11) : 833 -845 . DOI: 10.1007/s13238-013-3060-7

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