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Production of Bacillus anthracis protective antigen is dependent on the extracellular chaperone, PrsA

Lookup NU author(s): Rachel Williams, Dr Zoltan Pragai, Joanne Thwaite, Professor Peter Emmerson, Professor Colin Harwood

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Abstract

Protective antigen (PA) is a component of the Bacillus anthracis lethal and edema toxins and the basis of the current anthrax vaccine. In its heptameric form, PA targets host cells and internalizes the enzymatically active components of the toxins, namely lethal and edema factors. PA and other toxin components are secreted from B. anthracis using the Sec-dependent secretion pathway. This requires them to be translocated across the cytoplasmic membrane in an unfolded state and then to be folded into their native configurations on the trans side of the membrane, prior to their release from the environment of the cell wall. In this study we show that recombinant PA (rPA) requires the extracellular chaperone PrsA for efficient folding when produced in the heterologous host, B. subtilis; increasing the concentration of PrsA leads to an increase in rPA production. To determine the likelihood of PrsA being required for PA production in its native host, we have analyzed the B. anthracis genome sequence for the presence of genes encoding homologues of B. subtilis PrsA. We identified three putative B. anthracis PrsA proteins (PrsAA, PrsAB, and PrsAC) that are able to complement the activity of B. subtilis PrsA with respect to cell viability and rPA secretion, as well as that of AmyQ, a protein previously shown to be PrsA-dependent.


Publication metadata

Author(s): Williams RC, Rees ML, Jacobs MF, Pragai Z, Thwaite JE, Baillie LWJ, Emmerson PT, Harwood CR

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2003

Volume: 278

Issue: 20

Pages: 18056-18062

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M301244200

DOI: 10.1074/jbc.M301244200

PubMed id: 12606539


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