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Structure of E. coli Twin-arginine translocase (Tat) complex with bound cargo

Zhao, Z.; Sazanov, L.

2025-09-18 biochemistry
10.1101/2025.09.16.676506 bioRxiv
Show abstract

How the twin-arginine translocase (Tat) system transports fully folded substrate proteins across cellular membranes without disrupting membrane integrity has been a fundamental question in cell biology for decades. The Tat system recognizes cargo signal peptide via a conserved twin-arginine motif and is found in prokaryotes and plant organelles. Multi-subunit Tat complex facilitates proton motive force-dependent translocation process, yet its overall architecture remains unknown. Here, we present an atomic cryo-EM structure of a E. coli trimeric TatB3C3 complex bound to the substrate SufI. The complex adopts an unusual wide-open, bowl-shaped architecture with a polar inner cavity. Unexpectedly, the cargo is engaged in a dual-contact mode: while the signal peptide binds inside one TatBC unit, the folded domain docks tightly onto an adjacent unit. The structure offers a mechanistic framework for substrate engagement and translocation by the Tat system, suggesting a direct involvement of the entire Tat complex in substrate translocation.

Published in Molecular Cell (predicted rank #17) · training set

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