Burguete Alondra Schweizer, Fenn Timothy D, Brunger Axel T, Pfeffer Suzanne R
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2008 Jan 25;132(2):286-98. doi: 10.1016/j.cell.2007.11.048.
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.
GCC185是一种位于反式高尔基体网络的大型卷曲螺旋蛋白，它是接收来自晚期内体的运输小泡以及锚定从高尔基体发出的非中心体微管所必需的。在此，我们证明GCC185向高尔基体的募集是由Rab和Arl家族的两种定位于高尔基体的小GTP酶介导的。GCC185与Rab6结合，Rab结合所需残基的突变消除了高尔基体定位。与GCC185 Rab结合结构域结合的Rab6的晶体结构表明，Rab6识别紧邻C末端GRIP结构域的卷曲螺旋上的一个双重对称表面。出乎意料的是，Rab6结合促进了Arl1与GRIP结构域的结合。我们提出了一个双GTP酶膜附着的结构衍生模型，该模型突出了Rab GTP酶通过其无结构的、膜锚定的高变结构域在距膜相当远的距离处与结合伙伴结合的潜在能力。
