5E9D

RD-1 Mart-1 High bound to Mart-1 decameric peptide (ELA) in complex with HLA-A2

5E9D の概要

• エントリーDOI: 10.2210/pdb5e9d/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Melanoma derived Mart-1 peptide, ... (6 entities in total)
• 機能のキーワード: single chain tcr-pmhc complex, protein binding
• 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: 10
• 化学式量合計: 151790.60

構造登録者

Singh, N.K.,Baker, B.M. (登録日: 2015-10-15, 公開日: 2016-06-08, 最終更新日: 2024-11-06)

主引用文献

Harris, D.T.,Singh, N.K.,Cai, Q.,Smith, S.N.,Vander Kooi, C.W.,Procko, E.,Kranz, D.M.,Baker, B.M.
An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry.
Structure, 24:1142-1154, 2016

PubMed Abstract: Utilizing a diverse binding site, T cell receptors (TCRs) specifically recognize a composite ligand comprised of a foreign peptide and a major histocompatibility complex protein (MHC). To help understand the determinants of TCR specificity, we studied a parental and engineered receptor whose peptide specificity had been switched via molecular evolution. Altered specificity was associated with a significant change in TCR-binding geometry, but this did not impact the ability of the TCR to signal in an antigen-specific manner. The determinants of binding and specificity were distributed among contact and non-contact residues in germline and hypervariable loops, and included disruption of key TCR-MHC interactions that bias αβ TCRs toward particular binding modes. Sequence-fitness landscapes identified additional mutations that further enhanced specificity. Our results demonstrate that TCR specificity arises from the distributed action of numerous sites throughout the interface, with significant implications for engineering therapeutic TCRs with novel and functional recognition properties.

PubMed: 27238970
DOI: 10.1016/j.str.2016.04.011

実験手法

X-RAY DIFFRACTION (2.51 Å)