Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1
Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1
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DOI：
10.1038/nsmb714
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发表时间：
2004-01-01
影响因子：
16.8
通讯作者：
Song, HW
中科院分区：
文献类型：
--
作者：
Wu, MS;Lu, L;Song, HW
GRIP结构域golgins向trans-Golgi网络的募集由Arl 1介导，Arl 1是ARF/Arl小GTP酶家族的成员，通过它们的GRIP结构域和Arl 1-GTP之间的相互作用。与golgin-245的GRIP结构域复合的Arl 1-GTP的晶体结构显示Arl 1-GTP主要以疏水方式与GRIP结构域相互作用，开关II区域赋予主要识别表面。Arl 1-GTP和GRIP之间的相互作用中的开关和开关间区域的参与解释了GRIP结构域对Arl 1-GTP的特异性。已经在Arl 1-GTP和GRIP之间的界面上绘制了消除Arl 1介导的GRIP结构域高尔基体定位的突变。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Arl 1-GTP相互作用。破坏GRIP结构域二聚化的突变也废除了其高尔基体靶向，表明GRIP结构域的二聚体形式是一个功能单位。
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.