An allosteric site in the T-cell receptor Cß domain plays a critical signalling role.
Nat Commun
; 8: 15260, 2017 05 16.
Article
em En
| MEDLINE
| ID: mdl-28508865
ABSTRACT
The molecular mechanism through which the interaction of a clonotypic αß 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-Dd). 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 ß-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Transdução de Sinais
/
Receptores de Antígenos de Linfócitos T alfa-beta
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Regiões Determinantes de Complementaridade
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Sítio Alostérico
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article