6BJ2

TCR589 in complex with HIV(Pol448-456)/HLA-B35

6BJ2 の概要

• エントリーDOI: 10.2210/pdb6bj2/pdb
• 関連するPDBエントリー: 6BJ3 6BJ8
• 分子名称: TCR 589 alpha chain, TCR 589 beta chain, HLA class I histocompatibility antigen, B-35 alpha chain, ... (9 entities in total)
• 機能のキーワード: agonist, 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: 5
• 化学式量合計: 96017.01

構造登録者

Jude, K.M.,Sibener, L.V.,Garcia, K.C. (登録日: 2017-11-03, 公開日: 2018-07-25, 最終更新日: 2024-10-23)

主引用文献

Sibener, L.V.,Fernandes, R.A.,Kolawole, E.M.,Carbone, C.B.,Liu, F.,McAffee, D.,Birnbaum, M.E.,Yang, X.,Su, L.F.,Yu, W.,Dong, S.,Gee, M.H.,Jude, K.M.,Davis, M.M.,Groves, J.T.,Goddard III, W.A.,Heath, J.R.,Evavold, B.D.,Vale, R.D.,Garcia, K.C.
Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding.
Cell, 174:672-687.e27, 2018

PubMed Abstract: TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy.

PubMed: 30053426
DOI: 10.1016/j.cell.2018.06.017

実験手法

X-RAY DIFFRACTION (3.35 Å)