Roles of Asp179 and Glu270 in ADP-ribosylation of Actin by Clostridium perfringens Iota Toxin
Contributors: Tabakova, Irina Verfasser; Lang, Alexander E. Verfasser; Jank, Thomas 1976- Verfasser; Aktories, Klaus 1948- Verfasser; Albert-Ludwigs-Universität Freiburg Institut für Experimentelle und Klinische Pharmakologie und Toxikologie; Albert-Ludwigs-Universität Freiburg Freiburg Institute of Advanced Studies; Albert-Ludwigs-Universität Freiburg Centre for Biological Signalling Studies; Albert-Ludwigs-Universität Freiburg Fakultät für Chemie und Pharmazie; Albert-Ludwigs-Universität Freiburg
Publisher: Universität
Published: 2015
Place of publication: Freiburg
Language: eng
Subjects: Clostridium perfringens; ADP-Ribosylierung; Actin; Krebs; Onkologie
Description: Abstract: Clostridium perfringens iota toxin is a binary toxin composed of the enzymatically active component Ia and receptor binding component Ib. Ia is an ADP-ribosyltransferase, which modifies Arg177 of actin. The previously determined crystal structure of the actin-Ia complex suggested involvement of Asp179 of actin in the ADP-ribosylation reaction. To gain more insights into the structural requirements of actin to serve as a substrate for toxin-catalyzed ADP-ribosylation, we engineered Saccharomyces cerevisiae strains, in which wild type actin was replaced by actin variants with substitutions in residues located on the Ia-actin interface. Expression of the actin mutant Arg177Lys resulted in complete resistance towards Ia. Actin mutation of Asp179 did not change Ia-induced ADP-ribosylation and growth inhibition of S. cerevisiae. By contrast, substitution of Glu270 of actin inhibited the toxic action of Ia and the ADP-ribosylation of actin. In vitro transcribed/translated human β-actin confirmed the crucial role of Glu270 in ADP-ribosylation of actin by Ia
Notes: PLoS one. 10, 12 (2015), e0145708, DOI 10.1371/journal.pone.0145708, issn: 1932-6203

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