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  • Review Article
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The twin-arginine translocation (Tat) protein export pathway

Key Points

  • The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane of most bacteria and archaea. Proteins are targeted to the Tat machinery by signal peptides containing a conserved twin-arginine motif.

  • Some proteins need to be folded before transport because they contain redox cofactors that are inserted in the cytoplasm, or to avoid insertion of the incorrect metal ion cofactor at the active site. In some cases, dedicated chaperones ensure cofactor insertion before protein targeting to the Tat pathway.

  • Bacteria and archaea can have differential requirements for the Tat transport system. It is essential in some organisms, non-essential in others and completely absent in certain bacteria and archaea. Furthermore, the number of Tat substrates varies widely among different organisms.

  • The Escherichia coli Tat machinery comprises three proteins: TatA, TatB and TatC. The TatBC complex binds Tat substrate proteins through their signal peptides. TatA is recruited to the activated TatBC complex and mediates transport of the substrate.

  • TatA exists as monomers or small oligomers and polymerizes during Tat-mediated substrate transport. The transmembrane and amphipathic helices of TatA are essential regions of the protein, each undergoing self-interaction during TatA oligomerization.

  • TatA may form an aqueous channel through which substrate is transported or may deform the membrane to allow re-orientation of the polar phospholipid head groups around the substrate during transport.

Abstract

The twin-arginine translocation (Tat) protein export system is present in the cytoplasmic membranes of most bacteria and archaea and has the highly unusual property of transporting fully folded proteins. The system must therefore provide a transmembrane pathway that is large enough to allow the passage of structured macromolecular substrates of different sizes but that maintains the impermeability of the membrane to ions. In the Gram-negative bacterium Escherichia coli, this complex task can be achieved by using only three small membrane proteins: TatA, TatB and TatC. In this Review, we summarize recent advances in our understanding of how this remarkable machine operates.

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Figure 1: Physiological rationales for transporting proteins in a folded state using the Tat system.
Figure 2: Model for the Tat translocation cycle in E. coli and plant chloroplasts.
Figure 3: Structural and organizational features of Tat transporter components.

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Acknowledgements

The authors thank members of their laboratories, past and present, their collaborators and their colleagues in the Tat transport field for many insightful discussions on the Tat system, and apologize for being unable to cite many relevant papers owing to space constraints. Work in the authors' laboratories has been supported by the Biotechnology and Biological Sciences Research Council UK, the Medical Research Council UK, the Wellcome Trust, the Royal Society UK, the Leverhulme Trust, the European Molecular Biology Organization, the E. P. Abraham Cephalosporin Trust, the University of Oxford and the University of Dundee.

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Glossary

Signal peptides

Short, cleavable peptides that are usually found at the amino termini of proteins and direct their transport.

Halophilic

Living in a high-ionic-strength (salty) environment.

CuZ copper–sulphur cluster

The catalytic [4Cu–2S] cluster that is found at the active site of nitrous oxide reductase.

Metalloproteins

Protein that bind one or more metal ions either directly or as part of a more complex cofactor.

Signal anchor

A non-cleaved signal sequence.

Solution NMR

Structural analysis of a molecule in an aqueous solution by NMR spectroscopy.

Amphipathic helix

A protein helix that has one polar and one nonpolar face.

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Palmer, T., Berks, B. The twin-arginine translocation (Tat) protein export pathway. Nat Rev Microbiol 10, 483–496 (2012). https://doi.org/10.1038/nrmicro2814

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