Elucidation of Rab27 Recruitment by Its Effectors: Structure of Rab27a Bound to Exophilin4/Slp2-a

被引：46

作者：

Chavas, Leonard M. G. ^{[1
,2
]}

Ihara, Kentaro ^{[1
]}

Kawasaki, Masato ^{[1
]}

Torii, Seiji ^{[3
]}

Uejima, Tamami ^{[1
]}

Kato, Ryuichi ^{[1
]}

Izumi, Tetsuro ^{[3
]}

Wakatsuki, Soichi ^{[1
]}

机构：

[1] High Energy Accelerator Res Org KEK, Inst Mat Struct Sci, Struct Biol Res Ctr, Photon Factory, Tsukuba, Ibaraki 3050801, Japan

[2] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England

[3] Gunma Univ, Inst Mol & Cellular Regulat, Dept Mol Med, Maebashi, Gunma 3718512, Japan

来源：

STRUCTURE | 2008年 / 16卷 / 10期

关键词：

D O I：

10.1016/j.str.2008.07.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1468 / 1477

页数：10

共 39 条

[21] Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice [J].