Panic Bojana, Perisic Olga, Veprintsev Dmitry B, Williams Roger L, Munro Sean
MRC Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
Mol Cell. 2003 Oct;12(4):863-74. doi: 10.1016/s1097-2765(03)00356-3.
Golgins are large coiled-coil proteins that play a role in Golgi structure and vesicle traffic. The Arf-like GTPase Arl1 regulates the translocation of GRIP domain-containing golgins to Golgi membranes. We report here the 1.7 A resolution structure of human Arl1-GTP in a complex with the GRIP domain of golgin-245. The structure reveals that the GRIP domain consists of an S-shaped arrangement of three helices. The domain forms a homodimer that binds two Arl1-GTPs using two helices from each monomer. The structure is consistent with golgin-245 forming parallel coiled-coils and suggests how Arl1-GTP/GRIP complexes interact with Golgi membranes via the N termini of Arl1-GTP and the C-terminal tails of the GRIP domains. In cells, bivalent association with Arl1-GTP would increase residence time of the golgins on Golgi membranes. Despite no conservation of sequence, topology, or even helical direction, several other effectors form similar interactions with small GTPases via a pair of alpha helices, suggesting a common structural basis for effector recognition.
高尔基体蛋白是一类大型的卷曲螺旋蛋白，在高尔基体结构和囊泡运输中发挥作用。类Arf GTP酶Arl1调节含GRIP结构域的高尔基体蛋白向高尔基体膜的转运。我们在此报告人源Arl1-GTP与高尔基体蛋白245的GRIP结构域复合物的1.7埃分辨率结构。该结构显示，GRIP结构域由三个螺旋呈S形排列组成。该结构域形成一个同二聚体，每个单体用两个螺旋结合两个Arl1-GTP。该结构与高尔基体蛋白245形成平行卷曲螺旋一致，并提示了Arl1-GTP/GRIP复合物如何通过Arl1-GTP的N端和GRIP结构域的C端尾巴与高尔基体膜相互作用。在细胞中，与Arl1-GTP的二价结合会增加高尔基体蛋白在高尔基体膜上的停留时间。尽管在序列、拓扑结构甚至螺旋方向上都没有保守性，但其他几种效应器通过一对α螺旋与小GTP酶形成类似的相互作用，提示效应器识别存在共同的结构基础。
