Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase.
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.
Department of Physical Biochemistry, Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Alexey
A
Rak
Olena
O
Pylypenko
Thomas
T
Durek
Anja
A
Watzke
Susanna
S
Kushnir
Lucas
L
Brunsveld
Herbert
H
Waldmann
Roger S
RS
Goody
Kirill
K
Alexandrov
D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D050356:Lipid Metabolism; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017368:Protein Prenylation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D006153:Guanosine Diphosphate; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D008274:Magnesium