2gj6
The complex between TCR A6 and human Class I MHC HLA-A2 with the modified HTLV-1 TAX (Y5K-4-[3-Indolyl]-butyric acid) peptide
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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
2GJ6 is a Protein complex structure of sequences from Homo sapiens with SO4, 3IB and GOL 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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