PDBsum entry 2p5e

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protein ligands metals Protein-protein interface(s) links
Immune system PDB id
Protein chains
276 a.a. *
100 a.a. *
194 a.a. *
241 a.a. *
GOL ×8
SO4 ×5
Waters ×739
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structures of high affinity human t-cell receptors b pmhc reveal native diagonal binding geometry
Structure: Hla class i histocompatibility antigen, a-2 alpha chain: a. Fragment: extracellular domains alpha 1, alpha2 and alpha3, 25-299. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: beta-2 microglobulin, residues 21-119.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: b2m. Synthetic: yes. Other_details: this sequence occurs naturally in homo sapie
1.89Å     R-factor:   0.181     R-free:   0.236
Authors: M.Sami,P.J.Rizkallah,S.Dunn,Y.Li,R.Moysey,A.Vuidepot,E.Basto P.Todorov,P.Molloy,F.Gao,J.M.Boulter,B.K.Jakobsen
Key ref: M.Sami et al. (2007). 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. PubMed id: 17644531 DOI: 10.1093/protein/gzm033
15-Mar-07     Release date:   25-Sep-07    
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Protein chain
Pfam   ArchSchema ?
P01892  (1A02_HUMAN) -  HLA class I histocompatibility antigen, A-2 alpha chain
365 a.a.
276 a.a.
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
119 a.a.
100 a.a.*
Protein chain
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
194 a.a.*
Protein chain
No UniProt id for this chain
Struc: 241 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   15 terms 
  Biological process     immune system process   21 terms 
  Biochemical function     protein binding     3 terms  


DOI no: 10.1093/protein/gzm033 Protein Eng Des Sel 20:397-403 (2007)
PubMed id: 17644531  
Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry.
M.Sami, P.J.Rizkallah, S.Dunn, P.Molloy, R.Moysey, A.Vuidepot, E.Baston, P.Todorov, Y.Li, F.Gao, J.M.Boulter, B.K.Jakobsen.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21159619 D.H.Aggen, A.S.Chervin, F.K.Insaidoo, K.H.Piepenbrink, B.M.Baker, and D.M.Kranz (2011).
Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors.
  Protein Eng Des Sel, 24, 361-372.  
18767161 J.N.Haidar, B.Pierce, Y.Yu, W.Tong, M.Li, and Z.Weng (2009).
Structure-based design of a T-cell receptor leads to nearly 100-fold improvement in binding affinity for pepMHC.
  Proteins, 74, 948-960.  
19148199 K.C.Garcia, J.J.Adams, D.Feng, and L.K.Ely (2009).
The molecular basis of TCR germline bias for MHC is surprisingly simple.
  Nat Immunol, 10, 143-147.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
18809922 L.Derré, M.Bruyninx, P.Baumgaertner, M.Ferber, D.Schmid, A.Leimgruber, V.Zoete, P.Romero, O.Michielin, D.E.Speiser, and N.Rufer (2008).
Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues.
  Proc Natl Acad Sci U S A, 105, 15010-15015.  
  18424733 P.F.Robbins, Y.F.Li, M.El-Gamil, Y.Zhao, J.A.Wargo, Z.Zheng, H.Xu, R.A.Morgan, S.A.Feldman, L.A.Johnson, A.D.Bennett, S.M.Dunn, T.M.Mahon, B.K.Jakobsen, and S.A.Rosenberg (2008).
Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions.
  J Immunol, 180, 6116-6131.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.