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Crystal structure of Rab9 complexed to GDP reveals a dimer with an active conformation of switch II
Author(s) -
Wittmann Julia G,
Rudolph Markus G
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.05.004
Subject(s) - dimer , gtpase , rab , crystallography , chemistry , gtp' , stereochemistry , biophysics , biology , biochemistry , enzyme , organic chemistry
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 β‐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.