Non-classical protein secretion in bacteria.
BACKGROUND
We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function.


RESULTS
A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria.


CONCLUSIONS
We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online.
Bendtsen
Jannick D
JD
Center for Biological Sequence Analysis, BioCentrum-DTU, Building 208, Technical University of Denmark, DK-2800 Lyngby, Denmark. jannick@cbs.dtu.dk
Kiemer
Lars
L
Fausbøll
Anders
A
Brunak
Søren
S
D001120:Arginine / Q000378:metabolism; D001412:Bacillus subtilis / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D030562:Databases, Protein; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D021381:Protein Transport
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D001120:Arginine