1R5W

Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T-cell activation

Summary for 1R5W

• Entry DOI: 10.2210/pdb1r5w/pdb
• Descriptor: H-2 class II histocompatibility antigen, E-K alpha chain, MHC H2-IE-beta, artificial peptide (3 entities in total)
• Functional Keywords: tcr, mhc class ii, structural rearangement, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): P04224
• Total number of polymer chains: 6
• Total formula weight: 88320.59

Authors

Krogsgaard, M.,Prado, N.,Adams, E.,He, X.,Chow, D.C.,Wilson, D.B.,Garcia, K.C.,Davis, M.M. (deposition date: 2003-10-13, release date: 2004-03-02, Last modification date: 2024-11-06)

Primary citation

Krogsgaard, M.,Prado, N.,Adams, E.J.,He, X.L.,Chow, D.C.,Wilson, D.B.,Garcia, K.C.,Davis, M.M.
Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T cell activation
Mol.Cell, 12:1367-1378, 2003

PubMed Abstract: While in many cases the half-life of T cell receptor (TCR) binding to a particular ligand is a good predictor of activation potential, numerous exceptions suggest that other physical parameter(s) must also play a role. Accordingly, we analyzed the thermodynamics of TCR binding to a series of peptide-MHC ligands, three of which are more stimulatory than their stability of binding would predict. Strikingly, we find that during TCR binding these outliers show anomalously large changes in heat capacity, an indicator of conformational change or flexibility in a binding interaction. By combining the values for heat capacity (DeltaCp) and the half-life of TCR binding (t(1/2)), we find that we can accurately predict the degree of T cell stimulation. Structural analysis shows significant changes in the central TCR contact residue of the peptide-MHC, indicating that structural rearrangements within the TCR-peptide-MHC interface can contribute to T cell activation.

PubMed: 14690592
DOI: 10.1016/S1097-2765(03)00474-X

Experimental method

X-RAY DIFFRACTION (2.9 Å)