PXD070648

PXD070648 is an original dataset announced via ProteomeXchange.

Title	The resting and ligand-bound states of the membrane-embedded human T-cell receptor–CD3 complex
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-12-17
AnnouncementXML	Submission_2025-12-17_14:53:31.703.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	henrik molina
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	disulfide crosslinked residues
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-12 14:09:58	ID requested
⏵ 1	2025-12-17 14:53:32	announced

Dataset with its publication pending

submitter keyword: TCR2,disulfide bridge, membrane

Thomas Walz
contact affiliation	The Rockefeller University
contact email	twalz@rockefeller.edu
lab head
henrik molina
contact affiliation	THE ROCKEFELLER UNIVERSITY
contact email	henrik.molina@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070648
     1. Label: PRIDE project
     2. Name: The resting and ligand-bound states of the membrane-embedded human T-cell receptor–CD3 complex