Wegner A, Aktories K
Institute of Physiological Chemistry, Ruhr-University Bochum, Federal Republic of Germany.
J Biol Chem. 1988 Sep 25;263(27):13739-42.
The mode of action on actin polymerization of skeletal muscle actin ADP-ribosylated on arginine 177 by perfringens iota toxin was investigated. ADP-ribosylated actin decreased the rate of nucleated actin polymerization at substoichiometric ratios of ADP-ribosylated actin to monomeric actin. ADP-ribosylated actin did not tend to copolymerize with actin. Actin filaments were depolymerized by the addition of ADP-ribosylated actin. The maximal monomer concentration reached by addition of ADP-ribosylated actin was similar to the critical concentration of the pointed ends of actin filaments. ADP-ribosylated actin had no effect on the rate of polymerization of gelsolin-capped actin filaments which polymerize at the pointed ends. The results suggest that ADP-ribosylated actin acts as a capping protein which binds to the barbed ends of actin filaments to inhibit polymerization. Based on an analysis of the depolymerizing effect of ADP-ribosylated actin, the equilibrium constant for binding of ADP-ribosylated actin to the barbed ends of actin filaments was determined to be about 10(8) M-1. As actin is ADP-ribosylated by perfringens iota toxin and by botulinum C2 toxin, it appears that conversion of actin into a capping protein by ADP-ribosylation is a pathophysiological reaction catalyzed by bacterial toxins which ultimately leads to inhibition of actin assembly.
研究了产气荚膜梭菌iota毒素对精氨酸177位点ADP核糖基化的骨骼肌肌动蛋白肌动蛋白聚合作用的模式。在ADP核糖基化肌动蛋白与单体肌动蛋白的亚化学计量比下，ADP核糖基化肌动蛋白降低了有核肌动蛋白聚合的速率。ADP核糖基化肌动蛋白不倾向于与肌动蛋白共聚。通过添加ADP核糖基化肌动蛋白使肌动蛋白丝解聚。添加ADP核糖基化肌动蛋白达到的最大单体浓度与肌动蛋白丝尖端的临界浓度相似。ADP核糖基化肌动蛋白对在尖端聚合的凝溶胶蛋白封端的肌动蛋白丝的聚合速率没有影响。结果表明，ADP核糖基化肌动蛋白作为一种封端蛋白，与肌动蛋白丝的带刺末端结合以抑制聚合。基于对ADP核糖基化肌动蛋白解聚作用的分析，确定ADP核糖基化肌动蛋白与肌动蛋白丝带刺末端结合的平衡常数约为10(8) M-1。由于肌动蛋白可被产气荚膜梭菌iota毒素和肉毒杆菌C2毒素ADP核糖基化，因此ADP核糖基化将肌动蛋白转化为封端蛋白似乎是细菌毒素催化的一种病理生理反应，最终导致肌动蛋白组装的抑制。
