4JFH

High Affinity alpha24-beta17 T Cell Receptor for A2 HLA-Melanoma peptide complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

T-cell receptor specificity maintained by altered thermodynamics.

Madura, F.Rizkallah, P.J.Miles, K.M.Holland, C.J.Bulek, A.M.Fuller, A.Schauenburg, A.J.Miles, J.J.Liddy, N.Sami, M.Li, Y.Hossain, M.Baker, B.M.Jakobsen, B.K.Sewell, A.K.Cole, D.K.

(2013) J Biol Chem 288: 18766-18775

  • DOI: https://doi.org/10.1074/jbc.M113.464560
  • Primary Citation of Related Structures:  
    4JFD, 4JFE, 4JFF, 4JFH, 4JFO, 4JFP, 4JFQ

  • PubMed Abstract: 

    The T-cell receptor (TCR) recognizes peptides bound to major histocompatibility molecules (MHC) and allows T-cells to interrogate the cellular proteome for internal anomalies from the cell surface. The TCR contacts both MHC and peptide in an interaction characterized by weak affinity (KD = 100 nM to 270 μM). We used phage-display to produce a melanoma-specific TCR (α24β17) with a 30,000-fold enhanced binding affinity (KD = 0.6 nM) to aid our exploration of the molecular mechanisms utilized to maintain peptide specificity. Remarkably, although the enhanced affinity was mediated primarily through new TCR-MHC contacts, α24β17 remained acutely sensitive to modifications at every position along the peptide backbone, mimicking the specificity of the wild type TCR. Thermodynamic analyses revealed an important role for solvation in directing peptide specificity. These findings advance our understanding of the molecular mechanisms that can govern the exquisite peptide specificity characteristic of TCR recognition.


  • Organizational Affiliation

    Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
alpha24 TCR alleleA [auth D]200Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01848 (Homo sapiens)
Explore P01848 
Go to UniProtKB:  P01848
PHAROS:  P01848
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01848
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
beta17 TCR alleleB [auth E]244Homo sapiensMutation(s): 0 
UniProt
Find proteins for P01850 (Homo sapiens)
Explore P01850 
Go to UniProtKB:  P01850
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01850
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
H [auth D],
J [auth E],
K [auth E]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth D]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth D],
D,
E [auth D],
F [auth D],
I [auth E]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.14α = 90
b = 97.14β = 90
c = 123.08γ = 120
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
GDAdata collection
xia2data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-29
    Type: Initial release
  • Version 1.1: 2013-06-05
    Changes: Database references
  • Version 1.2: 2013-06-19
    Changes: Database references
  • Version 1.3: 2013-07-17
    Changes: Database references