1uxw
|
CRYSTAL STRUCTURE OF HLA-B*2709 COMPLEXED WITH THE LATENT MEMBRANE PROTEIN 2 PEPTIDE (LMP2) OF EPSTEIN-BARR VIRUS
OverviewOverview
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.
About this StructureAbout this Structure
1UXW is a Protein complex structure of sequences from Homo sapiens with GOL as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
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 Mon Nov 5 17:15:16 2007