9C3E

TCR - CD3 complex bound to HLA

Summary for 9C3E

• Entry DOI: 10.2210/pdb9c3e/pdb
• Related: 8TW4 8TW6 9BBC
• EMDB information: 45166
• Descriptor: TCRa, CHOLESTEROL, TCRb (EGFP fusion), ... (10 entities in total)
• Functional Keywords: t-cell receptor, tcr, 1g4, nanodisc, cd3, hla, ny-eso-1, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 277359.20

Authors

Notti, R.Q.,Walz, T. (deposition date: 2024-05-31, release date: 2024-10-02, Last modification date: 2024-10-16)

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.
Biorxiv, 2024

PubMed Abstract: The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). 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 . 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. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination.

PubMed: 37662363
DOI: 10.1101/2023.08.22.554360

Experimental method

ELECTRON MICROSCOPY (3.5 Å)