Wu Mousheng, Wang Tuanlao, Loh Eva, Hong Wanjin, Song Haiwei
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Proteos, Singapore.
EMBO J. 2005 Apr 20;24(8):1491-501. doi: 10.1038/sj.emboj.7600643. Epub 2005 Mar 31.
Rab7 regulates vesicle traffic from early to late endosomes, and from late endosomes to lysosomes. The crystal structure of Rab7-GTP in complex with the Rab7 binding domain of RILP reveals that Rab7 interacts with RILP specifically via two distinct areas, with the first one involving the switch and interswitch regions and the second one consisting of RabSF1 and RabSF4. Disruption of these interactions by mutations abrogates late endosomal/lysosomal targeting of Rab7 and RILP. The Rab7 binding domain of RILP forms a coiled-coil homodimer with two symmetric surfaces to interact with two separate Rab7-GTP molecules, forming a dyad configuration of Rab7-RILP(2)-Rab7. Mutations that disrupt RILP dimerization also abolish its interactions with Rab7-GTP and late endosomal/lysosomal targeting, suggesting that the dimeric form of RILP is a functional unit. Structural comparison suggests that the combined use of RabSF1 and RabSF4 with the switch regions may be a general mode of action for most Rab proteins in regulating membrane trafficking.
Rab7调节从早期内体到晚期内体以及从晚期内体到溶酶体的囊泡运输。Rab7-GTP与RILP的Rab7结合结构域形成复合物的晶体结构表明，Rab7通过两个不同区域与RILP特异性相互作用，第一个区域涉及开关区和开关间区域，第二个区域由RabSF1和RabSF4组成。通过突变破坏这些相互作用会消除Rab7和RILP的晚期内体/溶酶体靶向。RILP的Rab7结合结构域与两个对称表面形成卷曲螺旋同型二聚体，以与两个单独的Rab7-GTP分子相互作用，形成Rab7-RILP(2)-Rab7的二元结构。破坏RILP二聚化的突变也会消除其与Rab7-GTP的相互作用以及晚期内体/溶酶体靶向，这表明RILP的二聚体形式是一个功能单元。结构比较表明，RabSF1和RabSF4与开关区的联合使用可能是大多数Rab蛋白调节膜运输的一般作用模式。
