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Originally published In Press as doi:10.1074/jbc.M500071200 on February 16, 2005

J. Biol. Chem., Vol. 280, Issue 16, 16263-16271, April 22, 2005
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Anchor Structure of Staphylococcal Surface Proteins

V. ANCHOR STRUCTURE OF THE SORTASE B SUBSTRATE IsdC*

Luciano A. Marraffini{ddagger} and Olaf Schneewind§

From the Departments of §Microbiology and {ddagger}Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637

Staphylococcus aureus sortase A cleaves surface protein precursors bearing C-terminal LPXTG motif sorting signals between the threonine and glycine residues. Using lipid II precursor as cosubstrate, sortase A catalyzes the amide linkage between the carboxyl group of threonine and the amino group of pentaglycine cross-bridges, thereby tethering C-terminal ends of surface proteins to the bacterial cell wall envelope. Staphylococcal sortase B also anchors its only known substrate, the IsdC precursor with a C-terminal NPQTN motif sorting signal, to the cell wall envelope. Herein, we determined the cell wall anchor structure of IsdC. The sorting signal of IsdC is cleaved between threonine and asparagine of the NPQTN motif, and the carboxyl group of threonine is amide-linked to the amino group of pentaglycine crossbridges. In contrast to sortase A substrates, the anchor structure of IsdC displays shorter glycan strands and significantly less cell wall cross-linking. A model is proposed whereby sortases A and B recognize unique features of sorting signals and peptidoglycan substrates to deposit proteins with distinct topologies in the cell wall envelope.


Received for publication, January 4, 2005 , and in revised form, February 16, 2005.

* This work was supported by United States Public Health Service Grants AI38897 and AI52474 (to O. S.). This is Number V in the series "Anchor Structure of Staphylococcal Surface Proteins"; all of the preceding papers were published in the Journal of Biological Chemistry. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Microbiology, University of Chicago, 920 East 58th St., Chicago, IL 60637. Tel.: 773-834-9060; Fax: 773-834-8150; E-mail: oschnee{at}bsd.uchicago.edu.


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