2git: Difference between revisions
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'''Human Class I MHC HLA-A2 in complex with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide'''<br /> | '''Human Class I MHC HLA-A2 in complex with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide'''<br /> | ||
==Overview== | ==Overview== | ||
Although T cell receptor cross-reactivity is a fundamental property of the | Although T cell receptor cross-reactivity is a fundamental property of the immune system and is implicated in numerous autoimmune pathologies, the molecular mechanisms by which T cell receptors can recognize and respond to diverse ligands are incompletely understood. In the current study we examined the response of the human T cell lymphotropic virus-1 (HTLV-1) Tax-specific T cell receptor (TCR) A6 to a panel of structurally distinct haptens coupled to the Tax 11-19 peptide with a lysine substitution at position 5 (Tax5K, LLFG[K-hapten]PVYV). The A6 TCR could cross-reactively recognize one of these haptenated peptides, Tax-5K-4-(3-Indolyl)-butyric acid (IBA), presented by HLA-A*0201. The crystal structures of Tax5K-IBA/HLA-A2 free and in complex with A6 reveal that binding is mediated by a mechanism of cooperative conformational plasticity involving conformational changes on both sides of the protein-protein interface, including the TCR complementarity determining region (CDR) loops, Valpha/Vbeta domain orientation, and the hapten-modified peptide. Our findings illustrate the complex role that protein dynamics can play in TCR cross-reactivity and highlight that T cell receptor recognition of ligand can be achieved through diverse and complex molecular mechanisms that can occur simultaneously in the interface, not limited to molecular mimicry and CDR loop shifts. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2GIT 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 NA, GOL and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2GIT 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 <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GIT OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Baker, B | [[Category: Baker, B M.]] | ||
[[Category: Borbulevych, O | [[Category: Borbulevych, O Y.]] | ||
[[Category: FMT]] | [[Category: FMT]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:06 2008'' | ||
Revision as of 18:32, 21 February 2008
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Human Class I MHC HLA-A2 in complex with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide
OverviewOverview
Although T cell receptor cross-reactivity is a fundamental property of the immune system and is implicated in numerous autoimmune pathologies, the molecular mechanisms by which T cell receptors can recognize and respond to diverse ligands are incompletely understood. In the current study we examined the response of the human T cell lymphotropic virus-1 (HTLV-1) Tax-specific T cell receptor (TCR) A6 to a panel of structurally distinct haptens coupled to the Tax 11-19 peptide with a lysine substitution at position 5 (Tax5K, LLFG[K-hapten]PVYV). The A6 TCR could cross-reactively recognize one of these haptenated peptides, Tax-5K-4-(3-Indolyl)-butyric acid (IBA), presented by HLA-A*0201. The crystal structures of Tax5K-IBA/HLA-A2 free and in complex with A6 reveal that binding is mediated by a mechanism of cooperative conformational plasticity involving conformational changes on both sides of the protein-protein interface, including the TCR complementarity determining region (CDR) loops, Valpha/Vbeta domain orientation, and the hapten-modified peptide. Our findings illustrate the complex role that protein dynamics can play in TCR cross-reactivity and highlight that T cell receptor recognition of ligand can be achieved through diverse and complex molecular mechanisms that can occur simultaneously in the interface, not limited to molecular mimicry and CDR loop shifts.
DiseaseDisease
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 StructureAbout this Structure
2GIT is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
T cell receptor recognition via cooperative conformational plasticity., Gagnon SJ, Borbulevych OY, Davis-Harrison RL, Turner RV, Damirjian M, Wojnarowicz A, Biddison WE, Baker BM, J Mol Biol. 2006 Oct 13;363(1):228-43. Epub 2006 Aug 22. PMID:16962135
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