4JFQ: A2 Hla Complex With L8a Heteroclitic Variant Of Melanoma Peptide

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 mum). We used phage-display to produce a melanoma-specific TCR (alpha24beta17) 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, alpha24beta17 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.
PDB ID: 4JFQDownload
MMDB ID: 110556
PDB Deposition Date: 2013/2/28
Updated in MMDB: 2013/07
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4JFQ: trimeric; determined by author and by software (PISA)
Molecular Components in 4JFQ
Label Count Molecule
Proteins (3 molecules)
HLA Class I Histocompatibility Antigen, A-2 Alpha Chain(Gene symbol: HLA-A)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
L8A Heteroclitic Melanoma Peptide
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB