Crystal structure of Rab9 complexed to GDP reveals a dimer with an active conformation of switch II

FEBS Lett. 2004 Jun 18;568(1-3):23-9. doi: 10.1016/j.febslet.2004.05.004.

Abstract

The small GTPase Rab9 is an essential regulator of vesicular transport from the late endosome to the trans-Golgi network, as monitored by the redirection of the mannose-6-phosphate receptors. The crystal structure of Rab9 complexed to GDP, Mg(2+), and Sr(2+) reveals a unique dimer formed by an intermolecular beta-sheet that buries the switch I regions. Surface area and shape complementarity calculations suggest that Rab9 dimers can form an inactive, membrane-bound pool of Rab9 . GDP that is independent of GDI. Mg(2+)-bound Rab9 represents an inactive state, but Sr(2+)-bound Rab9 . GDP displays activated switch region conformations, mimicking those of the GTP state. A hydrophobic tetrad is formed resembling an effector-discriminating epitope found only in GTP-bound Rab proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Guanosine Diphosphate / chemistry
  • Guanosine Diphosphate / metabolism*
  • Metals / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • rab GTP-Binding Proteins / chemistry*
  • rab GTP-Binding Proteins / metabolism

Substances

  • Metals
  • Guanosine Diphosphate
  • RAB9A protein, human
  • rab GTP-Binding Proteins

Associated data

  • PDB/1S8F