Structure of doubly prenylated Ypt1:GDI complex and the mechanism of GDI-mediated Rab recycling.
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.
Pylypenko
Olena
O
Max-Planck-Institute for Molecular Physiology, Dortmund, Germany.
Rak
Alexey
A
Durek
Thomas
T
Kushnir
Susanna
S
Dursina
Beatrice E
BE
Thomae
Nicolas H
NH
Constantinescu
Alexandru T
AT
Brunsveld
Luc
L
Watzke
Anja
A
Waldmann
Herbert
H
Goody
Roger S
RS
Alexandrov
Kirill
K
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry*; D007425:Intracellular Membranes / Q000737:chemistry*; D008055:Lipids; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D012995:Solubility; D013816:Thermodynamics; D020691:rab GTP-Binding Proteins / Q000737:chemistry*
D048868:Adaptor Proteins, Signal Transducing; D020730:Guanine Nucleotide Dissociation Inhibitors; D008055:Lipids; C092439:MRS6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C064320:SEC4 protein, S cerevisiae; D020691:rab GTP-Binding Proteins