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molecular mechanism through which the interaction of a clonotypic \u03b1\u03b2 T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-D<sup>d</sup>). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR \u03b2-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the C\u03b2 H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays.","bibjson":{"author":[{"initials":"K","lastname":"Natarajan","name":"Natarajan K"},{"initials":"AC","lastname":"McShan","name":"McShan AC"},{"initials":"J","lastname":"Jiang","name":"Jiang J"},{"initials":"VK","lastname":"Kumirov","name":"Kumirov VK"},{"initials":"R","lastname":"Wang","name":"Wang R"},{"initials":"H","lastname":"Zhao","name":"Zhao H"},{"initials":"P","lastname":"Schuck","name":"Schuck P"},{"initials":"ME","lastname":"Tilahun","name":"Tilahun ME"},{"initials":"LF","lastname":"Boyd","name":"Boyd LF"},{"initials":"J","lastname":"Ying","name":"Ying J"},{"initials":"A","lastname":"Bax","name":"Bax A"},{"initials":"DH","lastname":"Margulies","name":"Margulies DH"},{"initials":"NG","lastname":"Sgourakis","name":"Sgourakis NG"}],"identifier":[{"id":"10.1038/ncomms15260","type":"doi"},{"id":"28508865","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Nat Commun","name":""},"pages":["15260"],"title":"An allosteric site in the T-cell receptor C\ufffd\ufffd domain plays a critical signalling role.","type":"article","url":"http://www.nature.com/articles/ncomms15260","volume":["8"],"year":[2017]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.10","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/5ivx"},"rcsb":{"url":"https://www.rcsb.org/structure/5ivx"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=5ivx"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":{"alpha":{"chains":["E"],"subgroup":"TRAV14"},"beta":{"chains":["F"],"subgroup":"TRBV29"},"mhc_type":"class_i","pdb_code":"5ivx"},"title":"H2-Dd presenting \"RGPGRAFVTI\" to Alpha/Beta T cell receptor at 2.10&#8491; resolution","unique_chain_count":5}}
