Hypothesis-review - An alternative model of the twin arginine translocation system

The twin arginine translocation (Tat) system is a machinery which can translocate folded proteins across energy transducing membranes. Currently it is supposed that Tat substrates bind directly to Tat translocon components before a DeltapH-driven translocation occurs. In this review, an alternative model is presented which proposes that membrane integration could precede Tat-dependent translocation. This idea is mainly supported by the recent observations of Tat-independent membrane insertion of Tat substrates in vivo and in vitro. Membrane insertion may allow i) a quality control of the folded state by membrane bound proteases like FtsH, ii) the recognition of the membrane spanning signal peptide by Tat system components, and iii) a pulling mechanism of translocation. In some cases of folded Tat substrates, the membrane targeting process may require ATP-dependent N-terminal unfolding-steps.