A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling |
| |
| Authors: | Luan P Heine A Zeng K Moyer B Greasely S E Kuhn P Balch W E Wilson I A |
| |
| Affiliation: | Department of Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA; Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA; Stanford Synchrotron Radiation Laboratory, Stanford University, Stanford, CA 94309, USA |
| |
| 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 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. |
| |
| Keywords: | fusion GDI Rab transport vesicle |
| 本文献已被 PubMed 等数据库收录！ |
|
