1uxw: Difference between revisions
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==Overview== | ==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 . | 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 Structure== | ==About this Structure== | ||
1UXW is a | 1UXW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UXW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: mhc (major histocompatibility complex)]] | [[Category: mhc (major histocompatibility complex)]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:33:27 2007'' | ||
Revision as of 15:28, 5 November 2007
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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
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