3D39

The complex between TCR A6 and human Class I MHC HLA-A2 with the modified HTLV-1 TAX (Y5(4-fluoroPhenylalanine)) peptide

3D39 の概要

• エントリーDOI: 10.2210/pdb3d39/pdb
• 関連するPDBエントリー: 1AO7 1QRN 1QSE 1QSF 2GJ6 3D3V
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Modified HTLV-1 TAX (Y5(4fluoro)F) peptide, ... (7 entities in total)
• 機能のキーワード: htlv-1 tax peptide, 4-fluorophenylalanine, mhc class i, hla-a2, t-cell receptor a6, glycoprotein, host-virus interaction, immune response, membrane, mhc i, phosphoprotein, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, immune system
• 由来する生物種: Homo sapiens; 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: 94622.75

構造登録者

Borbulevych, O.Y.,Clemens, J.R.,Baker, B.M. (登録日: 2008-05-09, 公開日: 2009-06-16, 最終更新日: 2023-08-30)

主引用文献

Piepenbrink, K.H.,Borbulevych, O.Y.,Sommese, R.F.,Clemens, J.,Armstrong, K.M.,Desmond, C.,Do, P.,Baker, B.M.
Fluorine substitutions in an antigenic peptide selectively modulate T-cell receptor binding in a minimally perturbing manner
Biochem.J., 423:353-361, 2009

PubMed Abstract: TCR (T-cell receptor) recognition of antigenic peptides bound and presented by MHC (major histocompatibility complex) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide-MHC complexes weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Furthermore, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. In the present study, we examined how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we found that fluorination of the Tax peptide [HTLV (human T-cell lymphotropic virus)-1 Tax(11-19)] enhanced binding by the Tax-specific TCR A6, yet weakened binding by the Tax-specific TCR B7. The changes in affinity were consistent with crystallographic structures and fluorine chemistry, and with the A6 TCR independent of other substitutions in the interface. Peptide fluorination thus provides a means to selectively modulate TCR binding affinity without significantly perturbing peptide composition or structure. Lastly, we probed the mechanism of fluorine's effect on TCR binding and we conclude that our results were most consistent with a 'polar hydrophobicity' mechanism, rather than a purely hydrophobic- or electrostatic-based mechanism. This finding should have an impact on other attempts to alter molecular recognition with fluorine.

PubMed: 19698083
DOI: 10.1042/BJ20090732

実験手法

X-RAY DIFFRACTION (2.81 Å)