Structure and mutational analysis of Rab GDP-dissociation inhibitor

• Published in: Nature (London) Vol. 381; no. 6577; pp. 42 - 48
• Main Authors: Schalk, Isabella, Zeng, Ke, Wu, Shih-Kwang, Stura, Enrico A, Matteson, Jeanne, Huang, Mingdong, Tandon, Anurag, Wilson, Ian A, Balch, William E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 02-05-1996; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing; Alkyl and Aryl Transferases; Amino Acid Sequence; Animals; Binding Sites; Biochemistry, Molecular Biology; Biological and medical sciences; Carrier Proteins; Carrier Proteins - chemistry; Cattle; Cellular biology; Conserved Sequence; Crystalline structure; Crystallography, X-Ray; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Guanine Nucleotide Dissociation Inhibitors; Humans; Life Sciences; Models, Molecular; Molecular biology; Molecular biophysics; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Binding; Protein Conformation; Protein Folding; rab GTP-Binding Proteins; rab3 GTP-Binding Proteins; Sequence Alignment; Structure in molecular biology; Structure-Activity Relationship; Bovine; Enzyme; Triphosphoric monoester hydrolases; dGTPase; Esterases; Vertebrata; Regulation(control); Mammalia; Three dimensional structure; Membrane transport; Hydrolases; Molecular complex; Artiodactyla; Ungulata; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/381042a0

The crystal structure of the bovine alpha-isoform of Rab GDP-dissociation inhibitor (GDI), which functions in vesicle-membrane transport to recycle and regulate Rab GTPases, has been determined to a resolution of 1.81 A. GDI is constructed of two main structural units, a large complex multisheet domain I and a smaller alpha-helical domain II. The structural organization of domain I is surprisingly closely related to FAD-containing monooxygenases and oxidases. Sequence-conserved regions common to GDI and the choroideraemia gene product, which delivers Rab to catalytic subunits of Rab geranylgeranyltransferase II, are clustered on one face of the molecule. The two most sequence-conserved regions, which form a compact structure at the apex of GDI, are shown by site-directed mutagenesis to play a critical role in the binding of Rab proteins.