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A New Functional Domain of Guanine Nucleotide Dissociation Inhibitor (α‐GDI) Involved in Rab Recycling
Author(s) -
Luan Peng,
Heine Andreas,
Zeng Ke,
Moyer Bryan,
Greasely Samantha E.,
Kuhn Peter,
Balch William E.,
Wilson Ian A.
Publication year - 2000
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2000.010309.x
Subject(s) - rab , gtpase , biology , microbiology and biotechnology , guanine nucleotide exchange factor , vesicular transport protein , biochemistry , transport protein , effector , biophysics , vesicle , membrane
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 α‐GDI at ultra‐high resolution (1.04 Å). Refinement at this resolution highlighted a region with high mobility of its main‐chain residues. This corresponded to a surface loop in the primarily α‐helical domain II at the base of α‐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 α‐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.