The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.

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-lip

SUBMITTER: Notti RQ 

PROVIDER: S-EPMC12708868 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature