PT  - JOURNAL ARTICLE
AU  - David L. Goldman
AU  - Edward Nieves
AU  - Antonio Nakouzi
AU  - Johanna Rivera
AU  - Ei Ei Phyu
AU  - Than Htut Win
AU  - Jacqueline Achkar
AU  - Arturo Casadevall
TI  - Serum-mediated cleavage of <em>Bacillus anthracis</em> Protective Antigen is a two-step process that involves a serum carboxypeptidase
AID  - 10.1101/267369
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 267369
4099  - http://biorxiv.org/content/early/2018/02/18/267369.short
4100  - http://biorxiv.org/content/early/2018/02/18/267369.full
AB  - Much our understanding of the activity of anthrax toxin is based on in-vitro systems, which delineate the interaction between B. anthracis toxins and the cell surface. These systems however, fail to account for the intimate association of B. anthracis with the circulatory system, including the contribution of serum proteins to the host response and processing of anthrax toxins. Using variety immunologic techniques to inhibit serum processing of B. anthracis Protective Antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments, similar to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysine residues from PA20.