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

Summary for 2GJ6

• Entry DOI: 10.2210/pdb2gj6/pdb
• Related: 1AO7 1DUZ 1QRN 1QSE 1QSF 2GIT
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Contains: Beta-2-microglobulin variant pI 5.3, Modified HTLV-1 TAX (Y5K-IBA) peptide, chain C, ... (9 entities in total)
• Functional Keywords: htlv-1 tax peptide, haptenated peptide, lysine-4-(3-indolyl)-butyric acid, mhc class i, hla-a2, t-cell receptor a6, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• Total number of polymer chains: 5
• Total formula weight: 96099.16

Authors

Borbulevych, O.Y.,Baker, B.M. (deposition date: 2006-03-30, release date: 2006-10-03, Last modification date: 2024-10-16)

Primary citation

Gagnon, S.J.,Borbulevych, O.Y.,Davis-Harrison, R.L.,Turner, R.V.,Damirjian, M.,Wojnarowicz, A.,Biddison, W.E.,Baker, B.M.
T Cell Receptor Recognition via Cooperative Conformational Plasticity.
J.Mol.Biol., 363:228-243, 2006

PubMed Abstract: 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.

PubMed: 16962135
DOI: 10.1016/j.jmb.2006.08.045

Experimental method

X-RAY DIFFRACTION (2.56 Å)