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 m144/beta2-microglobulin (beta2m) complex at 1.9A resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable alpha1, alpha2, and alpha3 domains. A unique disulfide bond links the alpha1 helix to the beta-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the alpha1 and alpha2 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 alpha2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding.
Natarajan
Kannan
K
Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Hicks
Ashleigh
A
Mans
Janet
J
Robinson
Howard
H
Guan
Rongjin
R
Mariuzza
Roy A
RA
Margulies
David H
DH
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016827:CD8 Antigens / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry; D002460:Cell Line; D018360:Crystallography, X-Ray; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000737:chemistry*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017385:Sequence Homology; D014764:Viral Proteins / Q000737:chemistry*; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D016827:CD8 Antigens; D002241:Carbohydrates; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; C489516:Tap2 protein, mouse; D014764:Viral Proteins; D001613:beta 2-Microglobulin; C105297:m144 protein, Mouse cytomegalovirus 1