STRUCTURE OF THE HUMAN ADP-RIBOSYLATION FACTOR-1 COMPLEXED WITH GDP
STRUCTURE OF THE HUMAN ADP-RIBOSYLATION FACTOR-1 COMPLEXED WITH GDP
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DOI：
10.1038/372704a0
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发表时间：
1994-12-15
期刊：
影响因子：
64.8
通讯作者：
RINGE, D
中科院分区：
文献类型：
--
作者：
AMOR, JC;HARRISON, DH;RINGE, D
adp核糖基化因子（ARFs）在真核生物中必不可少且普遍存在，参与囊泡运输，并作为磷脂酶D（文献1,2）和霍乱毒素（3,4）的激活剂发挥作用。ARF蛋白在膜运输和细胞器完整性方面的功能（5,6）与其与膜的可逆结合以及与膜磷脂的特异性相互作用密切相关。这些功能的一个共同特征是它们通过GTP的结合和水解来调节。在这里，我们报告了全长人ARF1 （M(r) 21,000）在其gdp绑定的非肉豆酰化形式的三维结构。独特的氨基末端α -螺旋和环的存在，以及Mg2+连接的差异和非结晶二聚体的存在，使该结构与其他gtp结合蛋白区别开来。这些特征为gtp依赖的膜亲和性调节、缺乏内在gtp酶活性以及效应结合表面的性质提供了结构基础。
ADP-ribosylation factors (ARFs) are essential and ubiquitous in eukaryotes, being involved in vesicular transport and functioning as an activator of phospholipase D (refs 1, 2) and cholera toxin(3,4). The functions of ARF proteins in membrane traffic and organelle integrity(5,6) are intimately tied to its reversible association with membranes and specific interactions with membrane phospholipids. One common feature of these functions is their regulation by the binding and hydrolysis of GTP. Here we report the three-dimensional structure of full-length human ARF1 (M(r) 21,000) in its GDP-bound non-myristoylated form. The presence of a unique amino-terminal alpha-helix and loop, together with differences in Mg2+ ligation and the existence of a non-crystallographic dimer, set this structure apart from other GTP-binding proteins. These features provide a structural basis for the GTP-dependent modulation of membrane affinity, the lack of intrinsic GTPase activity, and the nature of effector binding surfaces.