6UZ1

Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2

6UZ1 の概要

• エントリーDOI: 10.2210/pdb6uz1/pdb
• 分子名称: MHC class I antigen, A-2 alpha chain, Beta-2-microglobulin, LEU-LEU-PHE-GLY-TYR-PRO-VAL-TYR-VAL, ... (7 entities in total)
• 機能のキーワード: single-chain t cell receptor, peptide major histocompatibility complex, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 139082.73

構造登録者

Ma, J.,Singh, N.K. (登録日: 2019-11-14, 公開日: 2020-10-28, 最終更新日: 2024-10-30)

主引用文献

Singh, N.K.,Alonso, J.A.,Harris, D.T.,Anderson, S.D.,Ma, J.,Hellman, L.M.,Rosenberg, A.M.,Kolawole, E.M.,Evavold, B.D.,Kranz, D.M.,Baker, B.M.
An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.
Biochemistry, 59:4163-4175, 2020

PubMed Abstract: T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling.

PubMed: 33074657
DOI: 10.1021/acs.biochem.0c00689

実験手法

X-RAY DIFFRACTION (3.14 Å)