Cellular Expression and Crystal Structure of the Murine Cytomegalovirus Major Histocompatibility Complex Class I-like Glycoprotein, m153

J Biol Chem. 2007 Nov 30;282(48):35247-58. doi: 10.1074/jbc.M706782200. Epub 2007 Sep 26.

Abstract

Mouse cytomegalovirus (MCMV), a beta-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 major histocompatibility complex, class I (MHC-I) structure. Functions attributed to some family members include down-regulation of host MHC-I (m152) and NKG2D ligands (m145, m152, and 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 beta2m or peptide and is expressed at the surface of MCMV-infected cells. Its 2.4-A 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 N terminus. The structure provides a useful framework for comparative analysis of the divergent members of the m145 family.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray / methods
  • Drosophila
  • Fibroblasts / metabolism
  • Gene Expression Regulation*
  • Glycoproteins / chemistry*
  • Green Fluorescent Proteins / chemistry
  • Histocompatibility Antigens Class I / chemistry*
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Muromegalovirus / genetics*
  • NIH 3T3 Cells
  • Protein Conformation
  • Sequence Homology, Amino Acid

Substances

  • Glycoproteins
  • Histocompatibility Antigens Class I
  • Green Fluorescent Proteins

Associated data

  • PDB/2O5N