1sys

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spinqualitylabelsall models 1sys, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of HLA, B*4403, and peptide EEPTVIKKY

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

HLA class I polymorphism creates diversity in epitope specificity and T, cell repertoire. We show that HLA polymorphism also controls the choice of, Ag presentation pathway. A single amino acid polymorphism that, distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to, constitutively acquire peptides without any detectable incorporation into, the transporter associated with Ag presentation (TAP)-associated peptide, loading complex even under conditions of extreme peptide starvation. This, mode of peptide capture is less susceptible to viral interference than the, conventional loading pathway used by HLA-B*4402 that involves assembly of, class I molecules within the peptide loading complex. Thus, B*4402 and, B*4405 are at opposite extremes of a natural spectrum in HLA class I, dependence on the PLC for Ag presentation. These findings unveil a new, layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal, HLA class I loading versus effective pathogen evasion.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]

About this Structure

1SYS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion., Zernich D, Purcell AW, Macdonald WA, Kjer-Nielsen L, Ely LK, Laham N, Crockford T, Mifsud NA, Bharadwaj M, Chang L, Tait BD, Holdsworth R, Brooks AG, Bottomley SP, Beddoe T, Peh CA, Rossjohn J, McCluskey J, J Exp Med. 2004 Jul 5;200(1):13-24. Epub 2004 Jun 28. PMID:15226359

Page seeded by OCA on Mon Nov 12 19:18:19 2007