Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes
Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes
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DOI：
10.1016/j.jmb.2006.08.064
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发表时间：
2006-11-24
影响因子：
5.6
通讯作者：
Lambright, David G.
中科院分区：
文献类型：
--
作者：
Eathiraj, Sudharshan;Mishra, Ashwini;Lambright, David G.
Rab 11 GTdR调节内化质膜受体的再循环，并且对于胞质分裂的完成是必需的。Rab 11相互作用蛋白（FIPs）家族保留C-末端Rab-binding domain（RBD），选择性识别Rab 11的活性形式。胞质分裂的正常完成需要Rab 11和FIP 3之间的复合物。在这里，我们报告了组成型活性Rab 11和包含RBD的FIP 3构建体之间的异四聚体复合物的晶体结构和突变分析。两个Rab 11分子结合到FIP 3的C末端处的二联体对称位点，其形成具有张开的C末端和钩区域的非典型卷曲-卷曲二聚体。RBD与卷曲螺旋重叠。并延伸穿过C-端子钩。虽然FIP 3接合Rab 11的开关和开关间区域，但相互作用的模式与其他Rab-effector复合物的模式显著不同。特别地，开关11区域经历了从有序但非互补的活性构象到促进与FIP 3相互作用的重塑构象的大的结构重排。最后，我们提供的证据表明，FIP 3可以在细胞中形成同源寡聚体，Rab 11在体外结合的一个关键决定因素是必要的FIP 3招聘胞质分裂过程中回收内体。(c)2006爱思唯尔有限公司保留所有权利。
The Rab11 GTPase regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis. A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognize the active form of Rab11. Normal completion of cytokinesis requires a complex between Rab11 and FIP3. Here, we report the crystal structure and mutational analysis of a heterotetrameric complex between constitutively active Rab11 and a FIP3 construct that includes the RBD. Two Rab11 molecules bind to dyad symmetric sites at the C terminus of FIP3, which forms a non-canonical coiled-coiled dimer with a flared C terminus and hook region. The RBD overlaps with the coiled coil. and extends through the C-terminal hook. Although FIP3 engages the switch and interswitch regions of Rab11, the mode of interaction differs significantly from that of other Rab-effector complexes. In particular, the switch 11 region undergoes a large structural rearrangement from an ordered but non-complementary active conformation to a remodeled conformation that facilitates the interaction with FIP3. Finally, we provide evidence that FIP3 can form homo-oligomers in cells, and that a critical determinant of Rab11 binding in vitro is necessary for FIP3 recruitment to recycling endosomes during cytokinesis. (c) 2006 Elsevier Ltd. All rights reserved.