Rab and arl GTPase family members cooperate in the localization of the golgin GCC185
Rab and arl GTPase family members cooperate in the localization of the golgin GCC185
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DOI：
10.1016/j.cell.2007.11.048
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发表时间：
2008-01-25
期刊：
影响因子：
64.5
通讯作者：
Pfeffer, Suzanne R.
中科院分区：
文献类型：
--
作者：
Burguete, Alondra Schweizer;Fenn, Timothy D.;Pfeffer, Suzanne R.
GCC 185是一种位于高尔基体网络中的大卷曲螺旋蛋白，它是接受来自晚期内体的运输囊泡和锚定来自高尔基体的非中心体微管所必需的。在这里，我们证明了招募GCC 185的高尔基体介导的两个高尔基体本地化的小GTP酶的拉布和Arl家族。GCC 185结合Rab 6，Rab结合所需的残基的突变废除了高尔基体定位。Rab 6结合到GCC 185 Rab-binding结构域的晶体结构揭示Rab 6识别紧邻C-末端GRIP结构域的卷曲螺旋上的双重对称表面。出乎意料的是，Rab 6结合促进Arl 1与GRIP结构域的结合。我们提出了一个结构衍生的模型双GTP酶膜附着，突出了潜在的能力，拉布GTP酶达到结合伙伴在一个显着的距离从膜通过其非结构化和膜锚定，高变结构域。
GCC185 is a large coiled-coil protein at the trans Golgi network that is required for receipt of transport vesicles inbound from late endosomes and for anchoring noncentrosomal microtubules that emanate from the Golgi. Here, we demonstrate that recruitment of GCC185 to the Golgi is mediated by two Golgi-localized small GTPases of the Rab and Arl families. GCC185 binds Rab6, and mutation of residues needed for Rab binding abolishes Golgi localization. The crystal structure of Rab6 bound to the GCC185 Rab-binding domain reveals that Rab6 recognizes a two-fold symmetric surface on a coiled coil immediately adjacent to a C-terminal GRIP domain. Unexpectedly, Rab6 binding promotes association of Arl1 with the GRIP domain. We present a structure-derived model for dual GTPase membrane attachment that highlights the potential ability of Rab GTPases to reach binding partners at a significant distance from the membrane via their unstructured and membrane-anchored, hypervariable domains.