Article
- The EMBO Journal (2006) 25, 13 - 23
- doi:10.1038/sj.emboj.7600921
Published online: 5 January 2006
Subject Categories:
Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling
Olena Pylypenko, Alexey Rak, Thomas Dureka, Susanna Kushnir, Beatrice E Dursina, Nicolas H Thomaeb, Alexandru T Constantinescuc, Luc Brunsveld, Anja Watzke, Herbert Waldmann, Roger S Goody and Kirill Alexandrov
- Max-Planck-Institute for Molecular Physiology, Dortmund, Germany
Correspondence to:
Kirill Alexandrov, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund 44227, Germany. Tel.: +49 231 1332356; Fax: +49 231 1331651; E-mail: kirill.alexandrov@mpi-dortmund.mpg.de
aPresent address: Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA
bPresent address: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
cPresent address: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, Dresden 01307, Germany
Received 27 July 2005; Accepted 25 November 2005
Abstract
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.
Keywords:
- membrane extraction,
- protein prenylation,
- RabGDP dissociation inhibitor,
- RabGTPases,
- vesicular transport
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