title: A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling.
abstract: Guanine nucleotide dissociation inhibitor (GDI) is a 55-kDa protein that functions in vesicular membrane transport to recycle Rab GTPases. We have now determined the crystal structure of bovine alpha-GDI at ultra-high resolution (1.04 A). Refinement at this resolution highlighted a region with high mobility of its main-chain residues. This corresponded to a surface loop in the primarily alpha-helical domain II at the base of alpha-GDI containing the previously uncharacterized sequence-conserved region (SCR) 3A. Site-directed mutagenesis showed that this mobile loop plays a crucial role in binding of GDI to membranes and extraction of membrane-bound Rab. This domain, referred to as the mobile effector loop, in combination with Rab-binding residues found in the multi-sheet domain I at the apex of alpha-GDI may provide flexibility for recycling of diverse Rab GTPases. We propose that conserved residues in domains I and II synergize to form the functional face of GDI, and that domain II mediates a critical step in Rab recycling during vesicle fusion.
authors.affiliation: Department of Molecular Biology, Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: P
authors.initials: P
authors.lastname: Luan
authors.forename: A
authors.initials: A
authors.lastname: Heine
authors.forename: K
authors.initials: K
authors.lastname: Zeng
authors.forename: B
authors.initials: B
authors.lastname: Moyer
authors.forename: S E
authors.initials: SE
authors.lastname: Greasely
authors.forename: P
authors.initials: P
authors.lastname: Kuhn
authors.forename: W E
authors.initials: WE
authors.lastname: Balch
authors.forename: I A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D022161:Transport Vesicles / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D011993:Recombinant Fusion Proteins; D020761:rab1 GTP-Binding Proteins