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1uxw
From Proteopedia
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CRYSTAL STRUCTURE OF HLA-B*2709 COMPLEXED WITH THE LATENT MEMBRANE PROTEIN 2 PEPTIDE (LMP2) OF EPSTEIN-BARR VIRUS
Contents |
Overview
Molecular mimicry is discussed as a possible mechanism that may contribute to the development of autoimmune diseases. It could also be involved in the differential association of the human major histocompatibility subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These two subtypes differ only in residue 116 of the heavy chain (Asp in B(*)2705 and His in B(*)2709), but the reason for the differential disease association is not understood. Using x-ray crystallography, we show here that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the B(*)2705 and B(*)2709 molecules in two drastically deviating conformations. Extensive structural similarity between pLMP2 and the self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide type 1 receptor (residues 400-408)) is observed only when the peptides are presented by B(*)2705 because of a salt bridge between Arg(5) of both peptides and the subtype-specific heavy chain residue Asp(116). Combined with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell lines and clones, together with target cells presenting these peptides or a modified peptide analogue, our results reveal that a pathogen-derived peptide can exhibit major histocompatibility complex class I subtype-dependent, drastically distinct binding modes. Furthermore, the results demonstrate that molecular mimicry between pLMP2 and pVIPR in the HLA-B27 context is an allele-dependent property.
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
1UXW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes., Fiorillo MT, Ruckert C, Hulsmeyer M, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B, J Biol Chem. 2005 Jan 28;280(4):2962-71. Epub 2004 Nov 10. PMID:15537660
Page seeded by OCA on Thu Mar 20 14:38:20 2008
