Wu Mousheng, Lu Lei, Hong Wanjin, Song Haiwei
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609.
Nat Struct Mol Biol. 2004 Jan;11(1):86-94. doi: 10.1038/nsmb714. Epub 2003 Dec 29.
Recruitment of the GRIP domain golgins to the trans-Golgi network is mediated by Arl1, a member of the ARF/Arl small GTPase family, through interaction between their GRIP domains and Arl1-GTP. The crystal structure of Arl1-GTP in complex with the GRIP domain of golgin-245 shows that Arl1-GTP interacts with the GRIP domain predominantly in a hydrophobic manner, with the switch II region conferring the main recognition surface. The involvement of the switch and interswitch regions in the interaction between Arl1-GTP and GRIP accounts for the specificity of GRIP domain for Arl1-GTP. Mutations that abolished the Arl1-mediated Golgi localization of GRIP domain golgins have been mapped on the interface between Arl1-GTP and GRIP. Notably, the GRIP domain forms a homodimer in which each subunit interacts separately with one Arl1-GTP. Mutations disrupting the GRIP domain dimerization also abrogated its Golgi targeting, suggesting that the dimeric form of GRIP domain is a functional unit.
GRIP结构域高尔基蛋白向反式高尔基体网络的募集是由ARF/Arl小GTP酶家族成员Arl1介导的，通过它们的GRIP结构域与Arl1-GTP之间的相互作用实现。Arl1-GTP与高尔基体蛋白245的GRIP结构域形成复合物的晶体结构表明，Arl1-GTP主要以疏水方式与GRIP结构域相互作用，其中开关II区域提供主要的识别表面。开关区域和开关间区域参与Arl1-GTP与GRIP之间的相互作用，这解释了GRIP结构域对Arl1-GTP的特异性。已将消除Arl1介导的GRIP结构域高尔基蛋白高尔基体定位的突变定位在Arl1-GTP与GRIP之间的界面上。值得注意的是，GRIP结构域形成同源二聚体，其中每个亚基分别与一个Arl1-GTP相互作用。破坏GRIP结构域二聚化的突变也消除了其高尔基体靶向作用，这表明GRIP结构域的二聚体形式是一个功能单元。
