Cellular expression and crystal structure of the murine cytomegalovirus major histocompatibility complex class I-like glycoprotein, m153.
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.
Mans
Janet
J
Molecular Biology Section, Laboratory of Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
Natarajan
Kannan
K
Balbo
Andrea
A
Schuck
Peter
P
Eikel
Daniel
D
Hess
Sonja
S
Robinson
Howard
H
Simic
Hrvoje
H
Jonjic
Stipan
S
Tiemessen
Caroline T
CT
Margulies
David H
DH
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods; D004330:Drosophila; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics*; D041681:NIH 3T3 Cells; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D049452:Green Fluorescent Proteins