Structure and substrate recognition by the bacterial twin-arginine translocation (Tat) core complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• The twin-arginine translocation (Tat) system is a vital protein transport pathway across membranes, conserved across all domains of life.
• It plays crucial roles in bacterial virulence and plant photosynthesis by transporting folded proteins.
• The core complex, comprising TatA, TatB, and TatC proteins, mediates substrate binding and transport.

Purpose of the Study:

• To elucidate the structural mechanisms of the Tat transport system.
• To visualize the resting and substrate-bound states of Tat complexes from different organisms.
• To propose a model for the initial steps of Tat-mediated protein transport.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine high-resolution structures of Tat complexes.
• Biochemical and functional analyses were integrated with structural data.
• Structures were obtained for resting and substrate-bound states of TatBC and TatABC complexes.

Main Results:

• Structures of resting and substrate-bound TatBC and TatABC complexes were determined.
• Substrate proteins were shown to interact with the core complex via their N-terminal signal peptides.
• Tat targeting sequences contact TatC, while the peptide body is secured by TatB, and transmembrane helices thin the membrane.

Conclusions:

• The N-terminal signal peptide is the sole interaction point between substrate and the Tat core complex.
• Specific contacts between signal peptides and TatC/TatB mediate substrate recognition and clamping.
• The proposed model outlines the early mechanistic steps of Tat transport, involving membrane thinning and specific peptide interactions.