InterPro domain: IPR000806

Rab proteins, a family of small Ras-related GTP-binding proteins, are involved in regulation of intracellular vesicle trafficking [ 1 ]. Rab GDP dissociation inhibitor (GDI) forms a soluble complex with Rab proteins, thereby preventing exchange of GDP for GTP. Rab GDI exists in several isoforms, and belongs to the TCD/MRS6 family of GDP dissociation inhibitors.

The crystal structure of the bovine alpha-isoform of Rab GDI has beendetermined to a resolution of 1.81A [ 2 ]. 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 [ 3 ]. 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[ 3 ]. 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 [ 3 ].

1. 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
2. Structure and mutational analysis of Rab GDP-dissociation inhibitor. Nature 381, 42-8