Protein targeting by the bacterial twin-arginine translocation (Tat) pathway

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The Tat (twin-arginine translocation) protein export system is found in the cytoplasmic membrane of most prokaryotes and is dedicated to the transport of folded proteins. The Tat system is now known to be essential for many bacterial processes including energy metabolism, cell wall biosynthesis, the nitrogen-fixing symbiosis and bacterial pathogenesis. Recent studies demonstrate that substrate-specific accessory proteins prevent improperly assembled substrates from interacting with the Tat transporter. During the transport cycle itself substrate proteins bind to a receptor complex in the membrane which then recruits a protein-translocating channel to carry out the transport reaction.

Introduction

Prokaryotes possess two parallel and complementary pathways for the export of proteins across the cytoplasmic membrane. In the Sec pathway translocation occurs by a threading mechanism. This requires the substrate to be in an extended conformation. By contrast the more recently discovered Tat (twin-arginine translocation) pathway is dedicated to the transport of folded proteins. Proteins are targeted to the Tat pathway by N-terminal signal peptides harbouring consecutive, essentially invariant, arginine residues within an S–R–R–x–F–L–K consensus motif [1]. Subsequent protein translocation by the Tat apparatus is energised exclusively by the transmembrane proton electrochemical gradient (Δp) [2]. The Tat system is not restricted to prokaryotes but is also found in the thylakoid membrane of plant chloroplasts where it plays an essential role in the biogenesis of the photosynthetic electron-transport chain [3]. Here we summarize our current understanding of the bacterial Tat pathway with particular emphasis on recent discoveries. A more comprehensive general review of the Tat pathway in prokaryotes can be found in [4].

Section snippets

Tat substrates

The bacterial Tat pathway was originally recognized through its ability to transport proteins that bind cofactor molecules in the cytoplasm before export [1]. However, more recent studies show that the Tat system is equally important for the translocation of other types of proteins [5]. This can be illustrated by a consideration of the proteins now known to be exported by the Tat system of Escherichia coli where around a third of the Tat substrate proteins either appear to bind no cofactor or

Structure of Tat signal peptides

A common feature of peptide recognition by proteins is that the peptide only adopts a defined structure when in the bound state. Recent studies suggest that this precept is likely to apply to Tat signal peptides. The Tat signal peptide is disordered in the crystal structure of the Zymomonas mobilis glucose fructose oxidoreductase preprotein [25]. More importantly, solution NMR experiments show directly that the Tat signal peptide of Allochromatium vinosum high potential iron-sulfur protein is

Quality control on the Tat pathway

It is important that Tat substrates that either bind cofactors or oligomerise in the cytoplasm should be prevented from interacting with the export machinery until their assembly has been completed. An exciting recent development is the identification of substrate-specific proteins that appear to be involved in this type of quality control process. Two of these proteins are the homologous DmsD and TorD proteins which are involved, respectively, in the biogenesis of the molybdopterin-containing

Tat pathway components

In E. coli, the minimal components of the Tat translocation system are the integral membrane proteins TatA, TatB, and TatC [35, 36, 37, 38]. TatA and TatB are sequence-related proteins but perform distinct functions in the Tat pathway [36, 38]. Attempts to purify the Tat components from E. coli membranes have led to the identification of two distinct high molecular mass complexes containing multiple copies of their constituent Tat proteins. One essentially corresponds to TatA and the other

Tat mechanism

Recent in vitro studies of Tat translocation in E. coli and in pea thylakoids have provided substantive insight into the Tat transport cycle (Figure 3). Tat substrates are initially bound by the TatBC complex in an energy-independent step [41, 43, 50••]. Site-specific photoaffinity crosslinking experiments strongly suggest that TatC binds the consensus motif of the Tat signal peptide and, therefore, that TatC is the primary site of signal-peptide recognition in the Tat pathway [50••]. The

Conclusions

A combination of genomic analysis and physiological characterisation of tat mutants has started to reveal the wide diversity of substrates transported by the Tat system in different prokaryotes. Further surprises are likely as detailed studies of the Tat pathway in organisms other than E. coli are undertaken. In particular there is likely to be considerable interest in the role of the Tat pathway in the virulence of pathogenic bacteria.

The mechanism of Tat transport is especially intriguing

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We apologise to all those workers whose papers we have been unable to cite due to space constraints. We thank Dr Susan Lea for preparing Figure 1. We also thank all colleagues past and present with whom we have discussed the Tat system. Research in the authors’ laboratories is supported by the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC) and the Wellcome Trust. Tracy Palmer is an MRC senior non-clinical research fellow. Frank Sargent is a

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