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4JFF

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

Summary for 4JFF
Entry DOI10.2210/pdb4jff/pdb
Related4JFD 4JFE 4JFH 4JFO 4JFP 4JFQ
DescriptorHLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Melanoma motif, ... (8 entities in total)
Functional Keywordshla, tcr, melanoma motif, immune system, high affinity
Biological sourceHomo sapiens (human)
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Cellular locationMembrane; Single-pass type I membrane protein: P01892
Secreted: P61769
Total number of polymer chains5
Total formula weight95374.64
Authors
Rizkallah, P.J.,Cole, D.K.,Madura, F.,Sewell, A.K. (deposition date: 2013-02-28, release date: 2013-05-29, Last modification date: 2024-10-16)
Primary citationMadura, 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.
T-cell receptor specificity maintained by altered thermodynamics.
J.Biol.Chem., 288:18766-18775, 2013
Cited by
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.
PubMed: 23698002
DOI: 10.1074/jbc.M113.464560
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.43 Å)
Structure validation

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