Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling

被引：81

作者：

Pylypenko, O ^{[1
]}

Rak, A ^{[1
]}

Durek, T ^{[1
]}

Kushnir, S ^{[1
]}

Dursina, BE ^{[1
]}

Thomae, NH ^{[1
]}

Constantinescu, AT ^{[1
]}

Brunsveld, L ^{[1
]}

Watzke, A ^{[1
]}

Waldmann, H ^{[1
]}

Goody, RS ^{[1
]}

Alexandrov, K ^{[1
]}

机构：

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

来源：

EMBO JOURNAL | 2006年 / 25卷 / 01期

关键词：

membrane extraction; protein prenylation; RabGDP dissociation inhibitor; RabGTPases; vesicular transport;

D O I：

10.1038/sj.emboj.7600921

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：

In eukaryotic cells Rab/Ypt GTPases represent a family of key membrane traffic controllers that associate with their targeted membranes via C-terminally conjugated geranylgeranyl groups. GDP dissociation inhibitor (GDI) is a general and essential regulator of Rab recycling that extracts prenylated Rab proteins from membranes at the end of their cycle of activity and facilitates their delivery to the donor membranes. Here, we present the structure of a complex between GDI and a doubly prenylated Rab protein. We show that one geranylgeranyl residue is deeply buried in a hydrophobic pocket formed by domain II of GDI, whereas the other lipid is more exposed to solvent and is skewed across several atoms of the first moiety. Based on structural information and biophysical measurements, we propose mechanistic and thermodynamic models for GDI and Rab escort protein-mediated interaction of RabGTPase with intracellular membranes.

引用

页码：13 / 23

页数：11

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