Actin as the Substrate for ADP-ribosylation

ADP-ribosylation of actin depends on the native structure of the protein substrate. In the presence of EDTA, which chelates and removes the actin-bound magnesium ion, resulting in denaturation of actin, ADP-ribosylation is completely blocked (Just ef al., 1990). C. botulinum C2 toxin or C. perfringens iota toxin ADP-ribosylate monomeric G-actin, but not polymerized F-actin (Aktories et al., 1986b Schering et al., 1988). This is due to the fact that the acceptor amino acid arginine-177, which is located in domain III of actin, is at or near 

Actin-ADP-ribosylating Toxins Cytotoxic Mechanisms of Clostridium botulinum C2 Toxin and Clostridium perfringens lotaToxin 

Inhibition of nucleotion activity of the gelsolin-actin complex 

ADP-ribosylation completely blocks the actin ATPase activity and increases the rate of ATP exchange by about twofold (Geipel ef al., 1990 Geipel ef al., 1989). This effect is not due to inhibition of polymerization, because the basal ATPase activity of G-actin is also inhibited. Moreover, the ATPase activity of actin is blocked even in the quasi-monomeric actin-DNAse I complex after stimulation with the mycotoxin cytochalasin (Geipel ef al., 1990). Thus, by analogy with the ADP-ribosylation of G-proteins by cholera toxin, which inhibits G-protein-associated GTP hydrolysis, the ADP-ribosylation of actin inhibits its intrinsic ATPase activity. 

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