9GV7

Structure of reverse docking TCR in complex with peptide-HLA

9GV7 の概要

• エントリーDOI: 10.2210/pdb9gv7/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, Peptide, ... (7 entities in total)
• 機能のキーワード: tcr, hla, reverse docking, mhc, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 94715.30

構造登録者

Karuppiah, V. (登録日: 2024-09-23, 公開日: 2025-04-23, 最終更新日: 2025-04-30)

主引用文献

Powell, T.,Karuppiah, V.,Shaikh, S.A.,Pengelly, R.,Mai, N.,Barnbrook, K.,Sharma, A.,Harper, S.,Ebner, M.,Creese, A.J.
Determining T-cell receptor binding orientation and Peptide-HLA interactions using cross-linking mass spectrometry.
J.Biol.Chem., 301:108445-108445, 2025

PubMed Abstract: T cell receptors (TCRs) recognize specific peptides presented by human leukocyte antigens (HLAs) on the surface of antigen-presenting cells and are involved in fighting pathogens and cancer surveillance. Canonical docking orientation of TCRs to their target peptide-HLAs (pHLAs) is essential for T cell activation, with reverse binding TCRs lacking functionality. TCR binding geometry and molecular interaction footprint with pHLAs are typically obtained by determining the crystal structure. Here, we describe the use of a cross-linking tandem mass spectrometry (XL-MS/MS) method to decipher the binding orientation of several TCRs to their target pHLAs. Cross-linking sites were localized to specific residues and their molecular interactions showed differentiation between TCRs binding in canonical or reverse orientations. Structural prediction and crystal structure determination of two TCR-pHLA complexes validated these findings. The XL-MS/MS method described herein offers a faster and simpler approach for elucidating TCR-pHLA binding orientation and interactions.

PubMed: 40154610
DOI: 10.1016/j.jbc.2025.108445

実験手法

X-RAY DIFFRACTION (1.86 Å)