A new twist on an old pathway--accessory Sec [corrected] systems

Abstract

The export of proteins from their site of synthesis in the cytoplasm across the inner membrane is an important aspect of bacterial physiology. Because the location of extracytoplasmic proteins is ideal for host-pathogen interactions, protein export is also important to bacterial virulence. In bacteria, there are conserved protein export systems that are responsible for the majority of protein export: the general secretion (Sec) pathway and the twin-arginine translocation pathway. In some bacteria, there are also specialized export systems dedicated to exporting specific subsets of proteins. In this review, we discuss a specialized export system that exists in some Gram-positive bacteria and mycobacteria - the accessory Sec system. The common element to the accessory Sec system is an accessory SecA protein called SecA2. Here we present our current understanding of accessory Sec systems in Streptococcus gordonii, Streptococcus parasanguinis, Mycobacterium smegmatis, Mycobacterium tuberculosis and Listeria monocytogenes, making an effort to highlight apparent similarities and differences between the systems. We also review the data showing that accessory Sec systems can contribute to bacterial virulence.

Fig 1. Evolutionary relationships of SecA2 proteins

The phylogenetic tree was generated in MEGA4 using the Neighbor-Joining method. The length of the branches reflects the number of amino acid changes between different SecA2s, as indicated by the bar. Bootstrap values are shown at the junctions. SecA2 sequences were obtained by searching all bacterial genome and protein databases available from NCBI and TIGR (as of April 2008) for the term SecA. For organisms with two SecA sequences, the one least like B. subtilis SecA was defined as SecA2 and used to build the tree. For simplicity, only one species of Lactobacillus with a SecA2 is included on the tree. Organisms in red possess two SecY homologs.

Fig 2. Organization of accessory sec loci

Similar colouring indicates encoded proteins with homology or similar properties. Genes encoding SecA2-dependent substrates are in blue, glycosyltransferases in green, accessory Sec proteins in red, accessory SecA2-dependent secretion factors in orange. Any gene that does not fit in the above categories is white. Genes encoding proteins with predicted transmembrane domains are hatched.

Fig. 3. Domain organization of SecA2-dependent serine rich glycoproteins

Domains in full-length Fap1 and GspB are shown, with similar domains colour coded. Truncated GspB₇₃₆-FLAG is also depicted, and the GspB signal sequence is shown, including the location of critical glycine (G3) residues.

Fig. 4. Models for SecA2-dependent export

In the various accessory Sec systems, a SecA2-exported protein (shown in blue) might be exported either through a novel translocon or the canonical SecA1/SecYEG translocon with the assistance of SecA2. The example of a novel translocon is modelled on the SecA2/SecY2 system of S. gordonii, which is a candidate for this type of pathway.