3d2u
Structure of UL18, a Peptide-Binding Viral MHC Mimic, Bound to a Host Inhibitory Receptor
Structural highlights
FunctionUL18_HCMVA Plays a role in the protection against host NK cell cytotoxicity by interacting with and modulating the activity of the host inhibitory leukocyte Ig-like receptor 1/LILRB1, which is expressed on monocytes, dendritic cells, as well as subsets of T and NK cells. UL18 exerts an inhibitory effect on LIR-1+ NK cells, while it stimulates LIR-1- NK cell. These modulations prevent lysis of the infected cells by NK cells.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUL18 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. Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor.,Yang Z, Bjorkman PJ Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10095-100. Epub 2008 Jul 15. PMID:18632577[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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