5IVX

Crystal Structure of B4.2.3 T-Cell Receptor and H2-Dd P18-I10 Complex

Summary for 5IVX

• Entry DOI: 10.2210/pdb5ivx/pdb
• Related: 5IW1
• Descriptor: H-2 class I histocompatibility antigen, D-D alpha chain, Beta-2-microglobulin, T-CELL RECEPTOR ALPHA CHAIN, ... (7 entities in total)
• Functional Keywords: major histompatibility complex class i, mhc-i, h2-dd, h-2dd, t-cell receptor, tcr, b4.2.3, b423, immune response, viral immunoevasion, immune system, human immunodeficiency virus, molecular recognition
• Biological source: Mus musculus (Mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01900; Secreted: P01887
• Total number of polymer chains: 5
• Total formula weight: 93877.44

Authors

Natarajan, K.,Jiang, J.,Margulies, D. (deposition date: 2016-03-21, release date: 2017-03-29, Last modification date: 2024-10-16)

Primary citation

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.
An allosteric site in the T-cell receptor C beta domain plays a critical signalling role.
Nat Commun, 8:15260-15260, 2017

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). 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.

PubMed: 28508865
DOI: 10.1038/ncomms15260

Experimental method

X-RAY DIFFRACTION (2.1 Å)