title: A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria.
abstract: Surface proteins in gram-positive bacteria are frequently required for virulence, and many are attached to the cell wall by sortase enzymes. Bacteria frequently encode more than one sortase enzyme and an even larger number of potential sortase substrates that possess an LPXTG-type cell wall sorting signal. In order to elucidate the sorting pathways present in gram-positive bacteria, we performed a comparative analysis of 72 sequenced microbial genomes. We show that sortase enzymes can be partitioned into five distinct subfamilies based upon their primary sequences and that most of their substrates can be predicted by making a few conservative assumptions. Most bacteria encode sortases from two or more subfamilies, which are predicted to function nonredundantly in sorting proteins to the cell surface. Only approximately 20% of sortase-related proteins are most closely related to the well-characterized Staphylococcus aureus SrtA protein, but nonetheless, these proteins are responsible for anchoring the majority of surface proteins in gram-positive bacteria. In contrast, most sortase-like proteins are predicted to play a more specialized role, with each anchoring far fewer proteins that contain unusual sequence motifs. The functional sortase-substrate linkage predictions are available online (http://www.doe-mbi.ucla.edu/Services/Sortase/) in a searchable database.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, and the UCLA-DOE Center for Genomics and Proteomics, University of California, Los Angeles, California 90095-1570, USA.
authors.forename: David
authors.initials: D
authors.lastname: Comfort
authors.forename: Robert T
authors.initials: RT
authors.lastname: Clubb
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000145:classification / Q000235:genetics* / Q000502:physiology; D001426:Bacterial Proteins; D003546:Cysteine Endopeptidases; D016680:Genome, Bacterial; D023281:Genomics; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D005810:Multigene Family; D010802:Phylogeny; D013379:Substrate Specificity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases