4JFD

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

4JFD の概要

• エントリーDOI: 10.2210/pdb4jfd/pdb
• 関連するPDBエントリー: 4JFE 4JFF 4JFH 4JFO 4JFP 4JFQ
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Melanoma peptide, ... (8 entities in total)
• 機能のキーワード: hla, tcr, melanoma, immune system, high affinity, immunoglobulin
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 95312.35

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 (2.46 Å)