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From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis

Nature Reviews Microbiology volume 10, pages 213–225 (2012)Cite this article

Subjects

Key Points

  • In Gram-negative bacteria, substrates of the type V secretion pathway include a superfamily of proteins called autotransporters (ATs); these proteins are associated with a range of virulence functions, including adhesion, colonization, cell mobility, biofilm formation and cytotoxicity.

  • An understanding of how these proteins are delivered to the bacterial cell surface is crucial, as it could offer substantial biotechnical and biomedical benefits, including vaccine development through the secretion of unrelated target proteins.

  • Until recently, ATs were thought of as self-contained secretion systems. However, recent findings demonstrating that passenger domain secretion requires the aid of accessory factors, including the β-barrel assembly machinery (Bam) and several periplasmic chaperones, have challenged the perceived simplicity of AT secretion.

  • There have been several recent advances in our understanding of the molecular basis of AT biogenesis in Gram-negative bacteria, and we can now draw analogies between this process and outer-membrane protein (OMP) biogenesis.

  • These recent advances have also discovered common structural themes, translocation intermediates and accessory interactions during inner-membrane translocation, periplasmic transit and outer-membrane translocation of ATs. Furthermore, we have an improved understanding of the regulation of AT expression, the Bam complex, the driving force for passenger domain transport, and the cleavage of passenger domains after outer-membrane translocation.

Abstract

Autotransporters are a superfamily of proteins that use the type V secretion pathway for their delivery to the surface of Gram-negative bacteria. At first glance, autotransporters look to contain all the functional elements required to promote their own secretion: an amino-terminal signal peptide to mediate translocation across the inner membrane, a central passenger domain that is the secreted functional moiety, and a channel-forming carboxyl terminus that facilitates passenger domain translocation across the outer membrane. However, recent discoveries of common structural themes, translocation intermediates and accessory interactions have challenged the perceived simplicity of autotransporter secretion. Here, we discuss how these studies have led to an improved understanding of the mechanisms responsible for autotransporter biogenesis.

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Figure 1: Secretion mechanisms that constitute the type V secretion pathway.
Figure 2: Anatomy of the classical autotransporter structure.
Figure 3: Classical autotransporter biogenesis.
Figure 4: Models of passenger domain translocation across the outer membrane.
Figure 5: Mechanisms of passenger domain cleavage.

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Acknowledgements

We thank R. E. Fitzpatrick for helpful discussion and critical reading of the manuscript. This work was supported by the UK Medical Research Council and UK Biotechnology and Biological Sciences Research Council grants to I.R.H.

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Authors and Affiliations

  1. School of Immunity and Infection, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

    Denisse L. Leyton, Amanda E. Rossiter & Ian R. Henderson

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia

    Denisse L. Leyton

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  1. Denisse L. Leyton
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  2. Amanda E. Rossiter
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  3. Ian R. Henderson
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Correspondence to Denisse L. Leyton.

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Protein Data Bank

SUPPLEMENTARY INFORMATION

S1 (table)

Glossary

Translocation

The movement of proteins from one subcellular location to another (including movement to outside the cell).

Signal peptide

A short sequence found in nascent proteins that directs their transport to a particular subcellular location.

Signal peptidase

An endopeptidase that removes the signal peptide after protein translocation.

SPATE

Serine protease autotransporters from members of the family Enterobacteriaceae.

Lol pathway

A lipoprotein-specific sorting machinery that transfers lipoproteins from the inner membrane to the outer membrane.

Crosslink

To form a covalent bond between adjacent chains of a molecule.

POTRA domains

(Polypeptide transport-associated domains). Protein domains that are found in β-barrel assembly machinery protein A (BamA) family members.

Brownian ratchet

Directionally biased diffusion.

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Leyton, D., Rossiter, A. & Henderson, I. From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis. Nat Rev Microbiol 10, 213–225 (2012). https://doi.org/10.1038/nrmicro2733

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