Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor.
UL18 is a human cytomegalovirus class I MHC (MHCI) homolog that binds the host inhibitory receptor LIR-1 and the only known viral MHC homolog that presents peptides. The 2.2-A structure of a LIR-1/UL18/peptide complex reveals increased contacts and optimal surface complementarity in the LIR-1/UL18 interface compared with LIR/MHCI interfaces, resulting in a >1,000-fold higher affinity. Despite sharing only approximately 25% sequence identity, UL18's structure and peptide binding are surprisingly similar to host MHCI. The crystal structure suggests that most of the UL18 surface, except where LIR-1 and the host-derived light chain bind, is covered by carbohydrates attached to 13 potential N-glycosylation sites, thereby preventing access to bound peptide and association with most MHCI-binding proteins. The LIR-1/UL18 structure demonstrates how a viral protein evolves from its host ancestor to impede unwanted interactions while preserving and improving its receptor-binding site.
Yang
Zhiru
Z
Division of Biology 114-96 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Bjorkman
Pamela J
PJ
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003587:Cytomegalovirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D015789:HLA-A2 Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D036022:Capsid Proteins; D015789:HLA-A2 Antigen; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046912:Multiprotein Complexes; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C079750:VP23 protein, Human herpesvirus 1