Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase

被引：156

作者：

Rak, A

Pylypenko, O

Durek, T

Watzke, A

Kushnir, S

Brunsveld, L

Waldmann, H

Goody, RS

Alexandrov, K

机构：

[1] Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44227 Dortmund, Germany

[2] Max Planck Inst Mol Physiol, Dept Biol Chem, D-44227 Dortmund, Germany

[3] Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany

[4] Univ Dortmund, Dept Organ Chem, D-44227 Dortmund, Germany

来源：

SCIENCE | 2003年 / 302卷 / 5645期

关键词：

D O I：

10.1126/science.1087761

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Rab/Ypt guanosine triphosphatases (GTPases) represent a family of key membrane traffic regulators in eukaryotic cells whose function is governed by the guanosine diphosphate (GDP) dissociation inhibitor (RabGDI). Using a combination of chemical synthesis and protein engineering, we generated and crystallized the monoprenylated Ypt1: RabGDI complex. The structure of the complex was solved to 1.5 angstrom resolution and provides a structural basis for the ability of RabGDI to inhibit the release of nucleotide by Rab proteins. Isoprenoid binding requires a conformational change that opens a cavity in the hydrophobic core of its domain II. Analysis of the structure provides a molecular basis for understanding a RabGDI mutant that causes mental retardation in humans.

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页码：646 / 650

页数：5

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