A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling

Traffic. 2000 Mar;1(3):270-81. doi: 10.1034/j.1600-0854.2000.010309.x.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • Cytosol / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Guanine Nucleotide Dissociation Inhibitors / chemistry*
  • Guanine Nucleotide Dissociation Inhibitors / physiology
  • Intracellular Membranes / metabolism
  • Models, Molecular
  • Motion
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Transport
  • Recombinant Fusion Proteins / chemistry
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Structure-Activity Relationship
  • Transport Vesicles / metabolism
  • rab1 GTP-Binding Proteins / metabolism*


  • Fungal Proteins
  • GDP dissociation inhibitor 1
  • Guanine Nucleotide Dissociation Inhibitors
  • Recombinant Fusion Proteins
  • rab1 GTP-Binding Proteins