9C3E

TCR - CD3 complex bound to HLA

9C3E の概要

• エントリーDOI: 10.2210/pdb9c3e/pdb
• 関連するPDBエントリー: 8TW4 8TW6 9BBC
• EMDBエントリー: 45166
• 分子名称: TCRa, CHOLESTEROL, TCRb (EGFP fusion), ... (10 entities in total)
• 機能のキーワード: t-cell receptor, tcr, 1g4, nanodisc, cd3, hla, ny-eso-1, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 277359.20

構造登録者

Notti, R.Q.,Walz, T. (登録日: 2024-05-31, 公開日: 2024-10-02, 最終更新日: 2025-12-31)

主引用文献

Notti, R.Q.,Yi, F.,Heissel, S.,Bush, M.W.,Molvi, Z.,Das, P.,Molina, H.,Klebanoff, C.A.,Walz, T.
The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.
Nat Commun, 16:10996-10996, 2025

PubMed Abstract: The T-cell receptor (TCR) initiates T-lymphocyte activation, but the mechanism of TCR activation remains uncertain. Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the open and extended conformation seen in detergent, the unliganded TCR-CD3 in nanodiscs adopts two related closed and compacted conformations that represent its physiologic resting state in vivo. By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. These structures also reveal conformation-dependent protein-lipid and glycan-glycan interactions within the TCR. Together, these results establish allosteric conformational change during TCR activation, reveal avenues for immunotherapeutic engineering, and highlight the importance of native-like lipid environments for membrane protein structure determination.

PubMed: 41402338
DOI: 10.1038/s41467-025-66939-7

実験手法

ELECTRON MICROSCOPY (3.5 Å)