1im3

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Crystal Structure of the human cytomegalovirus protein US2 bound to the MHC class I molecule HLA-A2/tax

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Many persistent viruses have evolved the ability to subvert MHC class I, antigen presentation. Indeed, human cytomegalovirus (HCMV) encodes at, least four proteins that down-regulate cell-surface expression of class I., The HCMV unique short (US)2 glycoprotein binds newly synthesized class I, molecules within the endoplasmic reticulum (ER) and subsequently targets, them for proteasomal degradation. We report the crystal structure of US2, bound to the HLA-A2/Tax peptide complex. US2 associates with HLA-A2 at the, junction of the peptide-binding region and the alpha3 domain, a novel, binding surface on class I that allows US2 to bind independently of, peptide sequence. Mutation of class I heavy chains confirms the importance, of this binding site in vivo. Available data on class I-ER chaperone, interactions indicate that chaperones would not impede US2 binding., Unexpectedly, the US2 ER-luminal domain forms an Ig-like fold. A US2, structure-based sequence alignment reveals that seven HCMV proteins, at, least three of which function in immune evasion, share the same fold as, US2. The structure allows design of further experiments to determine how, US2 targets class I molecules for degradation.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]

About this Structure

1IM3 is a Protein complex structure of sequences from Homo sapiens and Human herpesvirus 5. Full crystallographic information is available from OCA.

Reference

Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2., Gewurz BE, Gaudet R, Tortorella D, Wang EW, Ploegh HL, Wiley DC, Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6794-9. PMID:11391001

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