9BBC

TCR GDN detergent micelle

Summary for 9BBC

• Entry DOI: 10.2210/pdb9bbc/pdb
• Related: 8TW4 8TW6
• EMDB information: 44417
• Descriptor: TCRa, CHOLESTEROL, TCRb, ... (10 entities in total)
• Functional Keywords: t-cell receptor, tcr, 1g4, nanodisc, cd3, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 186441.54

Authors

Notti, R.Q.,Walz, T. (deposition date: 2024-04-05, release date: 2024-10-02, Last modification date: 2025-12-31)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)