Crystal structure of the murine cytomegalovirus MHC-I homolog m144

Large DNA viruses of the herpesvirus family produce proteins that mimic host MHC-I molecules as part of their immunoevasive strategy. The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. To explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m.144/beta 2-microglobulin (beta 2m) complex at 1.9 angstrom resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable alpha 1, alpha.2, and alpha 3 domains. A unique disulfide bond links the alpha 1 helix to the beta-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the alpha 1 and alpha 2 helices and the lack of critical residues that normally contribute to anchoring the peptide N and C termini eliminates peptide binding. A region of 13 amino acid residues, corresponding to the amino-terminal portion of the alpha 2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding. Published by Elsevier Ltd.