The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain
The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain
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DOI：
10.1074/jbc.m104514200
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发表时间：
2001-11-09
影响因子：
4.8
通讯作者：
Ferreira, PA
中科院分区：
文献类型：
--
作者：
Cai, YF;Singh, BB;Ferreira, PA
Ran 结合蛋白 2 (RanBP2) 是一种脊椎动物镶嵌蛋白，由四个散布的 RanGTPase 结合结构域 (RBD)、可变且物种特异性锌指簇结构域、富含亮氨酸、亲环蛋白和亲环蛋白样 (CLD) 结构域组成。 RanBP2 的功能图谱表明，RBD1 和 RBD2 之间以及 RBD3 和 RBD4 之间的锌指结构域和 CLD 结构域分别与核输出受体 CRM1/exportin-1 和 26 S 蛋白酶体 19 S 调节颗粒的成分特异性相关。现在，我们报告了位于 RBD2 和 RBD3 之间的一个新的 RanBP2 结构域的映射，该结构域在部分重复的异构体 RanBP2L1 中也是保守的。然而，该结构域仅导致 RanBP2 与两种基于驱动蛋白微管的运动蛋白 KIF5B 和 KIF5C 的神经元关联。这些驱动蛋白在体外和体内与 RanBP2 直接结合。此外，驱动蛋白轻链和 RanGTPase 是该 RanBP2 宏装配复合体的一部分。这些数据提供了 RanBP2 中 KIF5B 和 KIF5C 特定对接位点的证据。出现了一个模型，其中 RanBP2 充当神经元核和细胞质运输途径的选择性信号整合器。
The Ran-binding protein 2 (RanBP2) is a vertebrate mosaic protein composed of four interspersed RanGTPase binding domains (RBDs), a variable and species-specific zinc finger cluster domain, leucine-rich, cyclophilin, and cyclophilin-like (CLD) domains. Functional mapping of RanBP2 showed that the domains, zinc finger and CLD, between RBD1 and RBD2, and RBD3 and RBD4, respectively, associate specifically with the nuclear export receptor, CRM1/exportin-1, and components of the 19 S regulatory particle of the 26 S proteasome. Now, we report the mapping of a novel RanBP2 domain located between RBD2 and RBD3, which is also conserved in the partially duplicated isoform RanBP2L1. Yet, this domain leads to the neuronal association of only RanBP2 with two kinesin microtubule-based motor proteins, KIF5B and KIF5C. These kinesins associate directly in vitro and in vivo with RanBP2. Moreover, the kinesin light chain and RanGTPase are part of this RanBP2 macroassembly complex. These data provide evidence of a specific docking site in RanBP2 for KIF5B and KIF5C. A model emerges whereby RanBP2 acts as a selective signal integrator of nuclear and cytoplasmic trafficking pathways in neurons.