bMERB domains are bivalent Rab8 family effectors evolved by gene duplication
bMERB domains are bivalent Rab8 family effectors evolved by gene duplication
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DOI：
10.7554/elife.18675
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发表时间：
2016-08-23
期刊：
影响因子：
7.7
通讯作者：
Mueller, Matthias P.
中科院分区：
文献类型：
--
作者：
Rai, Amrita;Oprisko, Anastasia;Mueller, Matthias P.
在它们的活性GTP结合形式中，Rab蛋白与称为效应分子的蛋白质相互作用。在这项研究中，我们已经彻底的特点是Rab效应结构域，是目前在蛋白质的Mical和EHBP家庭，都已知的行为内体运输。在我们的研究中，我们表明，这些效应器显示Rab8家族蛋白（Rab8，10，13和15）的偏好，一些效应器结构域可以通过单独的结合位点结合两个Rab蛋白。结构分析使我们能够解释对Rab8家族成员的特异性和两个相似的Rab结合位点的存在，这两个位点必须通过基因复制进化。这项研究是第一次彻底表征Rab效应蛋白，其在单个结构域内包含两个单独的Rab结合位点，允许Micals和EHBP同时结合两个Rab，从而表明这些效应分子在内体运输中的先前未知功能。
In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study, we have thoroughly characterized a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterize a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking.