Vogelsgesang Martin, Stieglitz Benjamin, Herrmann Christian, Pautsch Alex, Aktories Klaus
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany.
FEBS Lett. 2008 Apr 2;582(7):1032-6. doi: 10.1016/j.febslet.2008.02.051. Epub 2008 Mar 4.
C3-like toxins ADP-ribosylate and inactivate Rho GTPases. Seven C3-like ADP-ribosyltransferases produced by Clostridium botulinum, Clostridium limosum, Bacillus cereus and Staphylococcus aureus were identified and two representatives--C3bot from C. botulinum and C3stau2 from S. aureus--were crystallized. Here we present the 1.8A structure of C. limosum C3 transferase C3lim and compare it to the structures of other family members. In contrast to the structure of apo-C3bot, the canonical ADP-ribosylating turn turn motif is observed in a primed conformation, ready for NAD binding. This suggests an impact on the binding mode of NAD and on the transferase reaction. The crystal structure explains why auto-ADP-ribosylation of C3lim at Arg41 interferes with the ADP-ribosyltransferase activity of the toxin.
C3样毒素通过ADP-核糖基化作用使Rho GTPases失活。已鉴定出由肉毒梭菌、泥渣梭菌、蜡样芽孢杆菌和金黄色葡萄球菌产生的7种C3样ADP-核糖基转移酶，并使其中两个代表——来自肉毒梭菌的C3bot和来自金黄色葡萄球菌的C3stau2——结晶。本文我们展示了泥渣梭菌C3转移酶C3lim的1.8埃结构，并将其与其他家族成员的结构进行比较。与脱辅基C3bot的结构不同，在引发构象中观察到典型的ADP-核糖基化转角基序，准备好结合NAD。这表明对NAD的结合模式和转移酶反应有影响。晶体结构解释了为什么C3lim在Arg41处的自动ADP-核糖基化会干扰毒素的ADP-核糖基转移酶活性。
