C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins.
The family of C3-like exoenzymes comprises seven bacterial ADP-ribosyltransferases of different origin. The common hallmark of these exoenzymes is the selective N-ADP-ribosylation of the low molecular mass GTP-binding proteins RhoA, B, and C and inhibition of signal pathways controlled by Rho GTPases. Therefore, C3-like exoenzymes were applied as pharmacological tools for analyses of cellular functions of Rho protein in numerous studies. Recent structural and functional analyses of C3-like exoenzymes provide detailed information on the molecular mechanisms and functional consequences of ADP-ribosylation catalyzed by these toxins. More recently additional non-enzymatic actions of C3-like ADP-ribosyltransferases have been identified showing that C3 transferases from Clostridium botulinum and Clostridium limosum form a GDI-like complex with the Ras-like low molecular mass GTPase Ral without ADP-ribosylation. These results add novel information on the molecular mode of action(s) of C3-like exoenzymes and are discussed in this review.
Vogelsgesang
Martin
M
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-University Freiburg, Otto-Krayer-Haus, Albertstrasse 25, Freiburg, Germany.
Pautsch
Alexander
A
Aktories
Klaus
K
D036002:ADP Ribose Transferases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity; D020725:ral GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
D001427:Bacterial Toxins; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020725:ral GTP-Binding Proteins; D020741:rho GTP-Binding Proteins