The Mechanism of Tat-Dependent Protein Translocation

The twin-arginine translocation (Tat) system is the only general pathway for the transport of folded proteins across energized biological membranes. It is found in the bacterial or archaeal cytoplasmic membrane, the plant thylakoid membrane or the inner membrane of plant mitochondria. The biological importance of this translocation system can be exemplified by the fact that no bacterial or plant photosynthesis and photosynthetic oxygen evolvement would exist on earth without this system. Despite many biochemical and biophysical studies, the Tat mechanism has been puzzling since the system was discovered in the 1990ies. Important characteristics of the Tat system could not be explained, and also recent high-resolution structures of the Tat system’s core with bound substrate did not lead scientists to a general transport mechanism. In this integrative review, we attempt to answer the key open questions with relevance to the Tat mechanism and thereby develop the first comprehensive explanation of how folded proteins are translocated across membranes by the Tat system.