InterPro domain: IPR018203
General Information
- Identifier IPR018203
- Description GDP dissociation inhibitor
- Number of genes 574
- Gene duplication stats Loading...
- Associated GO terms GO:0005092 GO:0007264
Abstract
Rab proteins constitute a family of small GTPases that serve a regulatoryrole in vesicular membrane traffic [ 1 , 2 ]; C-terminal geranylgeranylation iscrucial for their membrane association and function. This post-translationalmodification is catalysed by Rab geranylgeranyl transferase (Rab-GGTase), a multi-subunit enzyme that contains a catalytic heterodimer and an accessorycomponent, termed Rab escort protein (REP)-1 [ 3 ]. REP-1 presents newly-synthesised Rab proteins to the catalytic component, and forms a stablecomplex with the prenylated proteins following the transfer reaction.
The mechanism of REP-1-mediated membrane association of Rab5 is similarto that mediated by Rab GDP dissociation inhibitor (GDI). REP-1 and Rab GDI also share other functional properties, including the ability to inhibit therelease of GDP and to remove Rab proteins from membranes.
The crystal structure of the bovine alpha-isoform of Rab GDI has beendetermined to a resolution of 1.81A [ 3 ]. The protein is composed of twomain structural units: a large complex multi-sheet domain I, and a smalleralpha-helical domain II.
The structural organisation of domain I is closely related to FAD-containingmonooxygenases and oxidases [ 4 ]. Conserved regions common to GDI and thechoroideraemia gene product, which delivers Rab to catalytic subunits ofRab geranylgeranyltransferase II, are clustered on one face of the domain[ 4 ]. The two most conserved regions form a compact structure at the apex ofthe molecule; site-directed mutagenesis has shown these regions to play acritical role in the binding of Rab proteins [ 4 ].
1. Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes. EMBO J. 13, 5262-73
2. Cloning of a brain-type isoform of human Rab GDI and its expression in human neuroblastoma cell lines and tumor specimens. Cancer Res. 55, 5445-50
3. Structure and mutational analysis of Rab GDP-dissociation inhibitor. Nature 381, 42-8