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Infection and Immunity, May 2004, p. 2710-2722, Vol. 72, No. 5
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.5.2710-2722.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
A Comparative Genome Analysis Identifies Distinct Sorting Pathways in Gram-Positive Bacteria
David Comfort and Robert T. Clubb*
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
Received 15 September 2003/
Returned for modification 25 November 2003/
Accepted 31 January 2004
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
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.
* Corresponding author. Mailing address: UCLA-DOE Center for Genomics and Proteomics, University of California, 405 Hilgard Ave., Los Angeles, CA 90095-1570. Phone: (310) 206-2334. Fax: (310) 206-4749. E-mail:
rclubb{at}mbi.ucla.edu.
Editor: V. J. DiRita
Infection and Immunity, May 2004, p. 2710-2722, Vol. 72, No. 5
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.5.2710-2722.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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