Download MendeleyAn allosteric site in the T-cell receptor C beta domain plays a critical signalling role.
Natarajan, K., McShan, A.C., Jiang, J., Kumirov, V.K., Wang, R., Zhao, H., Schuck, P., Tilahun, M.E., Boyd, L.F., Ying, J., Bax, A., Margulies, D.H., Sgourakis, N.G.(2017) Nat Commun 8: 15260-15260
- PubMed: 28508865
- DOI: https://doi.org/10.1038/ncomms15260
- Primary Citation of Related Structures:
5IVX, 5IW1 - PubMed Abstract:
The molecular mechanism through which the interaction of a clonotypic αβ 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 d ). 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 β-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cβ 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.
Organizational Affiliation:
Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
