Crystal structure of a dynamin GTPase domain in both nucleotide-free and GDP-bound forms
Crystal structure of a dynamin GTPase domain in both nucleotide-free and GDP-bound forms
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DOI：
10.1093/emboj/20.21.5813
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发表时间：
2001-11-01
期刊：
影响因子：
11.4
通讯作者：
Kull, FJ
中科院分区：
文献类型：
--
作者：
Niemann, HH;Knetsch, MLW;Kull, FJ
动力蛋白形成了一个多域gtp酶家族，参与内吞作用、囊泡运输和线粒体形态的维持。与经典的开关GTPases相反，一个力生成函数被建议用于动力蛋白。本文报道了Dictyostelium disideum dynamin a的无核苷酸和与gdp结合的GTPase结构域的2.3埃晶体结构，GTPase结构域是动力蛋白中最高度保守的区域。球形结构包含g蛋白核心折叠，通过插入55个氨基酸将其从6链延伸到8链。这种拓扑上独特的插入将动力蛋白与其他gtp结合蛋白亚家族区分开来。一个额外的n端螺旋与GTPase结构域的c端螺旋相互作用，形成一个疏水槽，可能被我们构建的动力蛋白的c端部分占据。在无核苷酸状态和GDP结合状态之间缺乏主要的构象变化，这表明动力蛋白的机械化学重排发生在GTP结合、GTP水解或磷酸盐释放期间，与GDP的损失无关。
Dynamins form a family of multidomain GTPases involved in endocytosis, vesicle trafficking and maintenance of mitochondrial morphology. In contrast to the classical switch GTPases, a force-generating function has been suggested for dynamins. Here we report the 2.3 Angstrom crystal structure of the nucleotide-free and GDP-bound GTPase domain of Dictyostelium discoideum dynamin A. The GTPase domain is the most highly conserved region among dynamins. The globular structure contains the G-protein core fold, which is extended from a six-stranded beta -sheet to an eight-stranded one by a 55 amino acid insertion. This topologically unique insertion distinguishes dynamins from other subfamilies of GTP-binding proteins. An additional N-terminal helix interacts with the C-terminal helix of the GTPase domain, forming a hydrophobic groove, which could be occupied by C-terminal parts of dynamin not present in our construct. The lack of major conformational changes between the nucleotide-free and the GDP-bound state suggests that mechanochemical rearrangements in dynamin occur during GTP binding, GTP hydrolysis or phosphate release and are not linked to loss of GDP.