Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 22, 2008 | Supplemental Material + Published
Journal Article Open

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

Abstract

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.

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, www.pdb.org (PDB ID code 3D2U). This article contains supporting information online at www.pnas.org/cgi/content/full/0804551105/DCSupplemental.

Attached Files

Published - YANpnas08.pdf

Supplemental Material - YANpnas08supp.pdf

Files

YANpnas08.pdf
Files (8.3 MB)
Name Size Download all
md5:2f1e2d91ae41f3558f28421c539ddd09
1.2 MB Preview Download
md5:9a9eb5705c499f176f8cb56f33d144cc
7.1 MB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 16, 2023