4JFD

Preservation of peptide specificity during TCR-MHC contact dominated affinity enhancement of a melanoma-specific TCR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.46 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

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
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chain276Homo sapiensMutation(s): 0 
Gene Names: HLA-AHLAA
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
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Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
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UniProt GroupP04439
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin100Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
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UniProt GroupP61769
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Melanoma peptide10N/AMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
High Affinity TCR Alpha Chain196Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01848 (Homo sapiens)
Explore P01848 
Go to UniProtKB:  P01848
PHAROS:  P01848
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UniProt GroupP01848
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
High Affinity TCR Beta Chain245Homo sapiensMutation(s): 0 
UniProt
Find proteins for P01850 (Homo sapiens)
Explore P01850 
Go to UniProtKB:  P01850
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UniProt GroupP01850
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TAM
Query on TAM

Download Ideal Coordinates CCD File 
F [auth A]TRIS(HYDROXYETHYL)AMINOMETHANE
C7 H17 N O3
GKODZWOPPOTFGA-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
I [auth A]
J [auth A]
K [auth A]
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth E],
M [auth E],
N [auth E],
O [auth E],
P [auth E],
Q [auth E]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.46 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 121.49α = 90
b = 121.49β = 90
c = 82.96γ = 90
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