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Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor
Lubker, Carolin Dove, Stefan Tang, Wei-Jen Bieber Urbauer, Ramona J. Moskovitz, Jackob Urbauer, Jeffrey L. Seifert, Roland
Lubker, Carolin
Dove, Stefan
Tang, Wei-Jen
Bieber Urbauer, Ramona J.
Moskovitz, Jackob
Urbauer, Jeffrey L.
Seifert, Roland
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Abstract
Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca2+-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth. Methionine (Met) residues in CaM, important for interactions between CaM and its binding partners, can be oxidized by ROS. We investigated the impact of site-specific oxidation of Met in CaM on EF activation using thirteen CaM-mutants (CaM-mut) with Met to leucine (Leu) substitutions. EF activation shows high resistance to oxidative modifications in CaM. An intact structure in the C-terminal region of oxidized CaM is sufficient for major EF activation despite altered secondary structure in the N-terminal region associated with Met oxidation. The secondary structures of CaM-mut were determined and described in previous studies from our group. Thus, excess cAMP production and the associated impairment of host defence may be afforded even under oxidative conditions in activated neutrophils.
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Date
2015-07-13
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MDPI
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Keywords
Bacillus anthracis edema factor, Adenylyl cyclase toxin, (Oxidized) calmodulin, (Oxidized) calmodulin mutants
Citation
Lübker, Carolin, Stefan Dove, Wei-Jen Tang, Ramona Urbauer, Jackob Moskovitz, Jeffrey Urbauer, and Roland Seifert. "Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus Anthracis Edema Factor." Toxins 7.7 (2015): 2598-614. doi:10.3390/toxins7072598.