4JFH

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

4JFH の概要

• エントリーDOI: 10.2210/pdb4jfh/pdb
• 関連するPDBエントリー: 4JFD 4JFE 4JFF 4JFO 4JFP 4JFQ
• 分子名称: alpha24 TCR allele, beta17 TCR allele, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: immunoglobulin, hla, tcr, melanoma, immune system, high affinity
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50250.48

構造登録者

Rizkallah, P.J.,Cole, D.K.,Madura, F.,Sewell, A.K. (登録日: 2013-02-28, 公開日: 2013-05-29, 最終更新日: 2024-10-30)

主引用文献

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.
T-cell receptor specificity maintained by altered thermodynamics.
J.Biol.Chem., 288:18766-18775, 2013

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

実験手法

X-RAY DIFFRACTION (2.4 Å)