GTP酶
拉布
GTP'
共价键
核苷酸
小型GTPase
化学
GTP结合蛋白调节剂
鸟苷二磷酸
生物物理学
G蛋白
生物化学
鸟苷三磷酸
生物
信号转导
酶
基因
有机化学
作者
David Luis Wiegandt,Sophie Vieweg,Frank T. Hofmann,Daniel Koch,Fu Li,Yao‐Wen Wu,Aymelt Itzen,Matthias Müller,Roger S. Goody
摘要
GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase-acryl-nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.
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