Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring
Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring
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DOI：
10.1038/8997
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发表时间：
1999-05-01
影响因子：
21.3
通讯作者：
McMahon, HT
中科院分区：
文献类型：
--
作者：
Stowell, MHB;Marks, B;McMahon, HT
GTPase Dynamin在内吞作用中起着至关重要的作用，它通过催化新生的囊泡从质膜上分裂出来。以预制的phosphatidylinositol-4，5-bisphosphate-containing脂纳米管作为动力蛋白自组装的膜模板，研究了动力蛋白在降解过程中的构象变化。电子显微镜显示，在GTP结合状态下，动力素环似乎紧密堆积在一起。GTP水解后，环间距增加了近两倍。当与纳米管结合时，Dynamin的GTPase活性是协同的，并且与未结合的Dynamin的活性相比增加了三个数量级。GTP水解的k(Cat)(但不是K-m)的增加解释了显著的协作性。这些数据表明，动力蛋白螺旋中一种新颖的、纵向的(类似弹簧的)构象变化可能参与了囊泡的分裂。
The GTPase dynamin plays an essential part in endocytosis by catalysing the fission of nascent clathrin-coated vesicles from the plasma membrane. Using preformed phosphatidylinositol-4,5-bisphosphate-containing lipid nanotubes as a membrane template for dynamin self-assembly, we investigate the conformational changes that arise during GTP hydrolysis by dynamin. Electron microscopy reveals that, in the GTP-bound state, dynamin rings appear to be tightly packed together. After GTP hydrolysis, the spacing between rings increases nearly twofold. When bound to the nanotubes, dynamin's GTPase activity is cooperative and is increased by three orders of magnitude compared with the activity of unbound dynamin. An increase in the k(cat) (but not the K-m) of GTP hydrolysis accounts for the pronounced cooperativity. These data indicate that a novel, lengthwise ('spring-like') conformational change in a dynamin helix may participate in vesicle fission.