Crystal structure of Rab9 complexed to GDP reveals a dimer with an active conformation of switch II.
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.
Wittmann
Julia G
JG
Department of Molecular Structural Biology and GZMB, Justus-von-Liebig-Weg 11, Georg-August University, 37077 Göttingen, Germany.
Rudolph
Markus G
MG
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D008670:Metals; D006153:Guanosine Diphosphate; C079856:RAB9A protein, human; D020691:rab GTP-Binding Proteins