Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
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DOI：
10.1016/s0092-8674(00)80670-4
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发表时间：
2000-02-04
期刊：
影响因子：
64.5
通讯作者：
Cerione, RA
中科院分区：
文献类型：
--
作者：
Hoffman, GR;Nassar, N;Cerione, RA
RhoGDI蛋白是Rho家族gtp结合蛋白的关键多功能调节剂。Cdc42/RhoGDI配合物的2.6埃x射线晶体结构揭示了GDI和Cdc42相互作用的两个重要位点。首先，GDI的氨基末端调控臂与Cdc42的开关I和II结构域结合，从而抑制GDP解离和GTP水解。其次，Cdc42的香叶基部分插入GDI分子免疫球蛋白样结构域内的疏水口袋，导致膜释放。结构数据表明gdi如何作为小gtp结合蛋白的负调节因子，以及类异戊二烯运动如何在这种关键的调节相互作用中被利用。
The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding proteins. The 2.6 Angstrom X-ray crystallographic structure of the Cdc42/RhoGDI complex reveals two important sites of interaction between GDI and Cdc42. First, the amino-terminal regulatory arm of the GDI binds to the switch I and II domains of Cdc42 leading to the inhibition of both GDP dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of Cdc42 inserts into a hydrophobic pocket within the immunoglobulin-like domain of the GDI molecule leading to membrane release. The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moeity is utilized in this critical regulatory interaction.