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Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor

Yang, Zhiru and Bjorkman, Pamela J. (2008) Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor. Proceedings of the National Academy of Sciences of the United States of America, 105 (29). pp. 10095-10100. ISSN 0027-8424. PMCID PMC2465803.

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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-Å 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 ≈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.

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URLURL TypeDescription CentralArticle
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2008 by The National Academy of Sciences of the USA. Freely available online through the PNAS open access option. 1. Contributed by Pamela J. Bjorkman, May 9, 2008 (sent for review April 24, 2008). Published online before print July 15, 2008, doi: 10.1073/pnas.0804551105. We thank Inder Nangiana and Peter Snow at the Caltech Protein Expression Center for assistance with expression of UL18, Yan Qi for setting up wild-type UL18/LIR-1 crystallization trials, David Mathog in the Caltech Sequence Analysis Facility for identifying potential UL18-binding peptides encoded by HCMV, and Tara Chapman-Arvedson and members of the P.J.B. laboratory for helpful discussions and critical reading of the manuscript. Z.Y. was supported by a Life Sciences Research Foundation Postdoctoral Fellowship (Howard Hughes Medical Institute Fellow). Author contributions: Z.Y. and P.J.B. designed research; Z.Y. performed research; Z.Y. and P.J.B. analyzed data; and Z.Y. and P.J.B. wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, (PDB ID code 3D2U). This article contains supporting information online at
Funding AgencyGrant Number
Life Sciences Research FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:cytomegalovirus; immune evasion; LIR-1; x-ray crystallography
Issue or Number:29
PubMed Central ID:PMC2465803
Record Number:CaltechAUTHORS:YANpnas08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11178
Deposited By: Archive Administrator
Deposited On:22 Jul 2008 04:01
Last Modified:03 Oct 2019 00:16

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