2PYE

Crystal Structures of High Affinity Human T-Cell Receptors Bound to pMHC RevealNative Diagonal Binding Geometry TCR Clone C5C1 Complexed with MHC

Summary for 2PYE

• Entry DOI: 10.2210/pdb2pye/pdb
• Related: 2BNR 2F53 2F54 2P5E 2P5W
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Cancer/testis antigen 1B, ... (10 entities in total)
• Functional Keywords: t-cell receptor, cdr3, phage display, mutant, high affinity, ny-eso-1, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769; Cytoplasm: P78358
• Total number of polymer chains: 5
• Total formula weight: 96013.35

Authors

Sami, M.,Rizkallah, P.J.,Dunn, S.,Li, Y.,Moysey, R.,Vuidepot, A.,Baston, E.,Todorov, P.,Molloy, P.,Gao, F.,Boulter, J.M.,Jakobsen, B.K. (deposition date: 2007-05-16, release date: 2007-09-25, Last modification date: 2024-10-16)

Primary citation

Sami, M.,Rizkallah, P.J.,Dunn, S.,Molloy, P.,Moysey, R.,Vuidepot, A.,Baston, E.,Todorov, P.,Yi, L.,Gao, F.,Boulter, J.M.,Jakobsen, B.K.
Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry
Protein Eng.Des.Sel., 20:397-403, 2007

PubMed Abstract: Naturally selected T-cell receptors (TCRs) are characterised by low binding affinities, typically in the range 1-100 microM. Crystal structures of syngeneic TCRs bound to peptide major histocompatibility complex (pMHC) antigens exhibit a conserved mode of binding characterised by a distinct diagonal binding geometry, with poor shape complementarity (SC) between receptor and ligand. Here, we report the structures of three in vitro affinity enhanced TCRs that recognise the pMHC tumour epitope NY-ESO(157-165) (SLLMWITQC). These crystal structures reveal that the docking mode for the high affinity TCRs is identical to that reported for the parental wild-type TCR, with only subtle changes in the mutated complementarity determining regions (CDRs) that form contacts with pMHC; both CDR2 and CDR3 mutations act synergistically to improve the overall affinity. Comparison of free and bound TCR structures for both wild-type and a CDR3 mutant reveal an induced fit mechanism arising from restructuring of CDR3 loops which allows better peptide binding. Overall, an increased interface area, improved SC and additional H-bonding interactions are observed, accounting for the increase in affinity. Most notably, there is a marked increase in the SC for the central methionine and tryptophan peptide motif over the native TCR.

PubMed: 17644531
DOI: 10.1093/protein/gzm033

Experimental method

X-RAY DIFFRACTION (2.3 Å)