Elucidation of Rab27 Recruitment by Its Effectors: Structure of Rab27a Bound to Exophilin4/Slp2-a
Elucidation of Rab27 Recruitment by Its Effectors: Structure of Rab27a Bound to Exophilin4/Slp2-a
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DOI：
10.1016/j.str.2008.07.015
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发表时间：
2008-10-08
期刊：
影响因子：
5.7
通讯作者：
Wakatsuki, Soichi
中科院分区：
文献类型：
--
作者：
Chavas, Leonard M. G.;Ihara, Kentaro;Wakatsuki, Soichi
Rab GTP酶通过与一组效应蛋白协作来协调真核细胞内的囊泡运输。Rab 27 a调节许多胞吐途径，其功能障碍导致Griscelli综合征人类免疫缺陷。Exophilin 4/Slp 2-a定位于富含磷脂酰丝氨酸的质膜上，并且其N-末端Rab 27结合结构域（RBD 27）在对接和融合之前特异性识别黑素体和分泌颗粒表面上的Rab 27。为了表征Rab 27与11种不同效应物的选择性结合，我们已经确定了Rab 27 a与Exophilin 4 RBD 27复合的1.8埃分辨率结构。效应器包装针对Rab 27 a的开关和开关间元件，并且对Rab 27 a的特异性亲和力通过效应器结构基序（S/T）（G/L）xW（F/Y）的方向变化来调节（2）。Rab 27 a和Exophilin 4相互作用表面之间观察到的结构互补揭示了Rab 27效应子之间的差异，并概述了其招募的一般机制。
Rab GTPases coordinate vesicular trafficking within eukaryotic cells by collaborating with a set of effector proteins. Rab27a regulates numerous exocytotic pathways, and its dysfunction causes the Griscelli syndrome human immunodeficiency. Exophilin4/Slp2-a localizes on phosphatidylserine-enriched plasma membrane, and its N-terminal Rab27-binding domain (RBD27) specifically recognizes Rab27 on the surfaces of melanosomes and secretory granules prior to docking and fusion. To characterize the selective binding of Rab27 to 11 various effectors, we have determined the 1.8 angstrom resolution structure of Rab27a in complex with Exophilin4 RBD27. The effector packs against the switch and interswitch elements of Rab27a, and specific affinity toward Rab27a is modulated by a shift in the orientation of the effector structural motif (S/T)(G/L)xW(F/Y)(2). The observed structural complementation between the interacting surfaces of Rab27a and Exophilin4 sheds light on the disparities among the Rab27 effectors and outlines a general mechanism for their recruitment.