Conformational cycle of a protease-containing ABC transporter in lipid nanodiscs reveals the mechanism of cargo-protein coupling.

ABSTRACT: Protease-containing ABC transporters (PCATs) couple the energy of ATP hydrolysis to the processing and export of diverse cargo proteins across cell membranes to mediate antimicrobial resistance and quorum sensing. Here, we combine biochemical analysis, single particle cryoEM, and DEER spectroscopy in lipid bilayers along with computational analysis to illuminate the structural and energetic underpinnings of coupled cargo protein export. Our integrated investigation uncovers competitive interplay between nucleotides and cargo protein binding that ensures the latter's orderly processing and subsequent transport. The energetics of cryoEM structures in lipid bilayers are congruent with the inferred mechanism from ATP turnover analysis and reveal a snapshot of a high-energy outward-facing confo

SUBMITTER: Zhang R 

PROVIDER: S-EPMC11491471 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature