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  • Review Article
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Emerging themes in SecA2-mediated protein export

Nature Reviews Microbiology volume 10, pages 779–789 (2012)Cite this article

Subjects

Key Points

  • The post-translational general secretion (Sec) pathway is powered by the essential ATPase SecA, which works with the SecYEG channel to translocate proteins across the cytoplasmic membrane.

  • Mycobacteria and some Gram-positive bacteria have two non-redundant SecA proteins, SecA1 and SecA2. SecA1 powers the essential canonical Sec pathway, whereas SecA2 mediates export of a limited set of proteins.

  • SecA2 export systems have diverse and important roles in cell envelope biogenesis and bacterial pathogenesis.

  • There are two types of SecA2 systems: SecA2–SecY2 systems and SecA2-only systems.

  • SecA2–SecY2 systems seem to operate mostly independent of the canonical Sec machinery as dedicated transporters of a group of serine-rich glycoproteins that function as adhesins. SecA2–SecY2 systems are encoded by a genomic locus that includes ORFs for glycosylation and export machinery.

  • SecA2-only systems do not contain a SecY2 or an obvious accessory membrane channel. Instead, SecA2-only systems seem to use the canonical SecYEG channel for exporting a diverse assortment of proteins.

  • It is unknown how SecA2 functions in comparison to the well-studied canonical SecA1 proteins. The same structural, biochemical and in vitro reconstitution analyses that have been used to understand canonical Sec-mediated export will surely prove valuable in answering the many mechanistic questions concerning SecA2–SecY2 and SecA2-only systems.

Abstract

The conserved general secretion (Sec) pathway carries out most protein export in bacteria and is powered by the essential ATPase SecA. Interestingly, mycobacteria and some Gram-positive bacteria possess two SecA proteins: SecA1 and SecA2. In these species, SecA1 is responsible for exporting most proteins, whereas SecA2 exports only a subset of substrates and is implicated in virulence. However, despite the impressive body of knowledge about the canonical SecA1, less is known concerning SecA2 function. Here, we review our current understanding of the different types of SecA2 systems and outline future directions for their study.

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Figure 1: Models of Sec export.
Figure 2: Domain organization of SecA2 proteins.
Figure 3: Organization of secA2 genomic loci.
Figure 4: SecA2–SecY2 system–targeting features.

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Acknowledgements

The authors thank members of the Braunstein laboratory for critical reading of this manuscript and N. Rigel for assistance with the graphic of the SecA1 structure in figure 2. Work on SecA2 in the Braunstein laboratory is supported by the US National Institutes of Health grant AI054540.

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  1. Department of Microbiology and Immunology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, 27599-27290, North Carolina, USA

    Meghan E. Feltcher & Miriam Braunstein

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Correspondence to Miriam Braunstein.

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Protein Data Bank

Glossary

Preproteins

Proteins that are synthesized with amino-terminal signal peptides for targeting to a particular cellular location.

Signal peptide

An amino-terminal amino acid sequence that is present on preproteins. The signal peptide helps target specific proteins for export out of the bacterial cytoplasm. Sec signal peptides are composed of a tripartite structure with a positively charged N terminus, a hydrophobic core and a signal-peptidase-cleavage site.

In vitro reconstitution

A technique for studying biochemical processes in vitro. Reconstitution of the Sec pathway in vitro involves incubation of preprotein and purified SecA with SecYEG-containing inverted membrane vesicles (IMVs). Preprotein translocation through SecYEG into an IMV is monitored by the loss of preprotein sensitivity to protease.

Glycosyltransferases

Enzymes that catalyse the post-translational addition of carbohydrate mono- or oligosaccharides onto acceptor molecules. Some glycosyl-transferases attach sugars to proteins to form glycoproteins. The sugar composition and structure of glycosyl modifications can be diverse.

O-linked glycosylation

A type of glycosylation in which a saccharide moiety is added to the hydroxyl oxygen of a serine or threonine residue.

Phagosome maturation

The process by which phagosomal vacuoles form around foreign particles or bacteria within a eukaryotic cell and ultimately fuse with lysosomes, resulting in a degradative phagolysosomal compartment.

Autolysin

A hydrolase that breaks the peptidoglycan matrix in the bacterial cell wall. Autolysins are important in bacterial cell growth and division.

S-layer

(Surface layer). An ordered array of protein subunits that form a lattice structure surrounding the bacterial cell wall. S-layers exist in many bacteria, as well as in many archaea. These protein layers serve as scaffolding structures for enzymes, contribute to cell surface adhesion and act as virulence factors, among other functions.

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Feltcher, M., Braunstein, M. Emerging themes in SecA2-mediated protein export. Nat Rev Microbiol 10, 779–789 (2012). https://doi.org/10.1038/nrmicro2874

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