TY  - JOUR
A1  - Angelika, Kronhardt
A1  - Rolando, Monica
A1  - Beitzinger, Christoph
A1  - Stefani, Caroline
A1  - Leuber, Michael
A1  - Flatau, Gilles
A1  - Popoff, Michel R.
A1  - Benz, Roland
A1  - Lemichez, Emmanuel
T1  - Cross-Reactivity of Anthrax and C2 Toxin: Protective Antigen Promotes the Uptake of Botulinum C2I Toxin into Human Endothelial Cells
T2  - PLoS ONE
N2  - Binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the AB(7/8) type of toxins. The B subunits bind both host cell receptors and the enzymatic A polypeptides to trigger their internalization and translocation into the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase (C2I) and C2II binding subunits. Anthrax toxin is composed of adenylate cyclase (EF) and MAPKK protease (LF) enzymatic components associated to protective antigen (PA) binding subunit. The binding and translocation components anthrax protective antigen (PA(63)) and C2II of C2 toxin share a sequence homology of about 35%, suggesting that they might substitute for each other. Here we show by conducting in vitro measurements that PA(63) binds C2I and that C2II can bind both EF and LF. Anthrax edema factor (EF) and lethal factor (LF) have higher affinities to bind to channels formed by C2II than C2 toxin's C2I binds to anthrax protective antigen (PA(63)). Furthermore, we could demonstrate that PA in high concentration has the ability to transport the enzymatic moiety C2I into target cells, causing actin modification and cell rounding. In contrast, C2II does not show significant capacity to promote cell intoxication by EF and LF. Together, our data unveiled the remarkable flexibility of PA in promoting C2I heterologous polypeptide translocation into cells.
KW  - Lipid bilayer-membranes
KW  - Current noise-analysis
KW  - Matrix protein porin
KW  - Clostridium-botulinum
KW  - Lethal factor
KW  - Edema factor
KW  - Escherichia-coli
KW  - Crystal-structure
KW  - Ion-channel
KW  - Phenylalanine clamp
Y1  - 2011
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/13479
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-134791
VL  - 6
IS  - 8
ER  -