TCR in nanodisc ND-IITCR in nanodisc ND-II

Structural highlights

8tw6 is a 8 chain structure with sequence from Escherichia coli str. K-12 substr. MG1655, Homo sapiens and Human orthopneumovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.1Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD3E_HUMAN The CD3 complex mediates signal transduction.

Publication Abstract from PubMed

The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( 1-4 ). 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( 5-8 ), 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. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination.

The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.,Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. doi: , 10.1101/2023.08.22.554360. PMID:37662363[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T. The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex. bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. PMID:37662363 doi:10.1101/2023.08.22.554360

8tw6, resolution 3.10Å

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