Mans, Janet and Natarajan, Kannan and Balbo, Andrea and Schuck, Peter and Eikel, Daniel and Hess, Sonja and Robinson, Howard and Šimić, Hrvoje and Jonjić, Stipan and Tiemessen, Caroline T. and Margulies, David H. (2007) Cellular expression and crystal structure of the murine cytomegalovirus MHC-Iv glycoprotein, m153. Journal of Biological Chemistry, 282 (48). pp. 35247-35258. ISSN 0021-9258 http://resolver.caltech.edu/CaltechAUTHORS:MANjbc07
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Mouse cytomegalovirus (MCMV), a β-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. MCMV encodes the m145 family of putative immunoevasins with predicted MHC-I structure. Functions attributed to some family members include downregulation of host MHC-I (m152) and NKG2D ligands (m145, m152, m155) and interaction with inhibitory or activating NK receptors (m157). We present the cellular, biochemical and structural characterization of m153, which is a heavily glycosylated homodimer, that does not require β2m or peptide, and is expressed at the surface of MCMV-infected cells. Its 2.4 Å crystal structure confirms that this compact molecule preserves an MHC-I-like fold and reveals a novel mode of dimerization, confirmed by site-directed mutagenesis, and a distinctive disulfide-stabilized extended amino terminus. The structure provides a useful framework for comparative analysis of the divergent members of the m145 family.
|Additional Information:||Copyright © 2007 by the American Society for Biochemistry and Molecular Biology. Received for publication, August 14, 2007, and in revised form, September 13, 2007. Originally published In Press as doi:10.1074/jbc.M706782200 on September 26, 2007. The atomic coordinates and structure factors (code 2O5N) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). This work was supported in part by the Intramural Research Program of NIAID and NIDDK, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The online version of this article (available at http://www.jbc.org) contains supplemental "Experimental Procedures," Figs. S1-S5, and Table S1. [J.M. was] [s]upported by a predoctoral fellowship from the National Institutes of Health and the Polio Research Foundation of South Africa. [C.T.T. was the] [r]ecipient of a Wellcome Trust senior international research fellowship (076352/Z/05/Z). We thank Barbara Newman and Rose Mage for production of rabbit antiserum, members of the Molecular Biology Section, Laboratory of Immunology, NIAID, NIH for their help, and Sam Xiao and Jack Bennink for comments on the manuscript. Support for beamline X29 of the National Synchrotron Light Source comes principally from the Offices of Biological and Environmental Research and of Basic Energy Sciences of the U.S. Department of Energy and from the National Center for Research Resources of the National Institutes of Health.|
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|Deposited On:||11 Oct 2007|
|Last Modified:||26 Dec 2012 09:44|
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