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首页> 外文期刊>Journal of Molecular Biology >Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin.
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Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin.

机译：梭状芽胞杆菌致死性毒素对Ha-Ras进行单糖基化的结构后果。

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摘要

Mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin at effector region threonine 35 has diverse effects on the Ras GTPase cycle, the dominant one of which is the inhibition of Ras-Raf coupling, leading to complete blockade of Ras downstream signaling. To understand the structural basis of the functional consequences of glucosylation, the X-ray crystal structure of glucosylated Ras-GDP was compared with that of non-modified Ras. Glucosylated Ras exhibits a different crystal packing but the overall three-dimensional structure is not altered. The glucose group does not affect the conformation of the effector loop. Due to steric constraints, the glucose moiety prevents the formation of the GTP conformation of the effector loop, which is a prerequisite for binding to the Raf-kinase. The X-ray crystal data also revealed the alpha-anomeric configuration of the bound glucose, indicating that the glucose transfer proceeds under retention of the C-1 configuration of the d-alpha-glucose. Therefore, glucosylation preserves the inactive conformation of the effector loop independently of the nucleotide occupancy, leading to a complete inhibition of downstream signaling of Ras. Copyright 2000 Academic Press.
机译：Sodellii致命毒素在效应子苏氨酸35上对Ha-Ras的单葡糖基化作用对Ras GTPase循环具有多种影响，其中主要的作用之一是抑制Ras-Raf偶联，从而完全阻断Ras下游信号传导。为了了解糖基化功能后果的结构基础，将糖基化Ras-GDP的X射线晶体结构与未修饰的Ras进行了比较。糖基化的Ras表现出不同的晶体堆积，但整体三维结构没有改变。葡萄糖基团不影响效应子环的构象。由于空间限制，葡萄糖部分阻止了效应子环的GTP构象的形成，这是结合Raf激酶的先决条件。 X射线晶体数据还揭示了结合的葡萄糖的α-异头构型，表明葡萄糖转移在保留d-α-葡萄糖的C-1构型下进行。因此，糖基化独立于核苷酸占据而保留了效应子环的非活性构象，从而导致对Ras下游信号的完全抑制。版权所有2000学术出版社。

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