Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 24 October 2003:
Vol. 302. no. 5645, pp. 646 - 650
DOI: 10.1126/science.1087761
Prev | Table of Contents | Next

Reports

Structure of Rab GDP-Dissociation Inhibitor in Complex with Prenylated YPT1 GTPase

Alexey Rak,1 Olena Pylypenko,3 Thomas Durek,1 Anja Watzke,2 Susanna Kushnir,1 Lucas Brunsveld,2 Herbert Waldmann,2,4 Roger S. Goody,1 Kirill Alexandrov1*

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.

1 Department of Physical Biochemistry, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
2 Department of Chemical Biology, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
3 Department of Biomolecular Mechanisms, Max-Planck-Institut for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
4 Department of Organic Chemistry, University of Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.

* To whom correspondence should be addressed. E-mail: kirill.alexandrov{at}mpi-dortmund.mpg.de

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structure of the Disordered C Terminus of Rab7 GTPase Induced by Binding to the Rab Geranylgeranyl Transferase Catalytic Complex Reveals the Mechanism of Rab Prenylation.
Y.-W. Wu, R. S. Goody, R. Abagyan, and K. Alexandrov (2009)
J. Biol. Chem. 284, 13185-13192
   Abstract »    Full Text »    PDF »
UNC-108/Rab2 Regulates Postendocytic Trafficking in Caenorhabditis elegans.
D. K. Chun, J. M. McEwen, M. Burbea, and J. M. Kaplan (2008)
Mol. Biol. Cell 19, 2682-2695
   Abstract »    Full Text »    PDF »
A Structural Model of the GDP Dissociation Inhibitor Rab Membrane Extraction Mechanism.
A. Ignatev, S. Kravchenko, A. Rak, R. S. Goody, and O. Pylypenko (2008)
J. Biol. Chem. 283, 18377-18384
   Abstract »    Full Text »    PDF »
Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators.
Y.-W. Wu, K.-T. Tan, H. Waldmann, R. S. Goody, and K. Alexandrov (2007)
PNAS 104, 12294-12299
   Abstract »    Full Text »    PDF »
Rabs and their effectors: Achieving specificity in membrane traffic.
B. L. Grosshans, D. Ortiz, and P. Novick (2006)
PNAS 103, 11821-11827
   Abstract »    Full Text »    PDF »
Protein structure database search and evolutionary classification.
J.-M. Yang and C.-H. Tung (2006)
Nucleic Acids Res. 34, 3646-3659
   Abstract »    Full Text »    PDF »
The Hsp90 Chaperone Complex Regulates GDI-dependent Rab Recycling.
C. Y. Chen and W. E. Balch (2006)
Mol. Biol. Cell 17, 3494-3507
   Abstract »    Full Text »    PDF »
Thematic review series: Lipid Posttranslational Modifications. Geranylgeranylation of Rab GTPases.
K. F. Leung, R. Baron, and M. C. Seabra (2006)
J. Lipid Res. 47, 467-475
   Abstract »    Full Text »    PDF »
Structural Clues to Rab GTPase Functional Diversity.
S. R. Pfeffer (2005)
J. Biol. Chem. 280, 15485-15488
   Abstract »    Full Text »    PDF »
Autoinhibition of p50 Rho GTPase-activating Protein (GAP) Is Released by Prenylated Small GTPases.
P. Moskwa, M.-H. Paclet, M.-C. Dagher, and E. Ligeti (2005)
J. Biol. Chem. 280, 6716-6720
   Abstract »    Full Text »    PDF »
Human RAS Superfamily Proteins and Related GTPases.
J. Colicelli (2004)
Sci. STKE 2004, re13
   Abstract »    Full Text »    PDF »
The Structural GDP/GTP Cycle of Rab11 Reveals a Novel Interface Involved in the Dynamics of Recycling Endosomes.
S. Pasqualato, F. Senic-Matuglia, L. Renault, B. Goud, J. Salamero, and J. Cherfils (2004)
J. Biol. Chem. 279, 11480-11488
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)