2WM9

Structure of the complex between DOCK9 and Cdc42.

Summary for 2WM9

• Entry DOI: 10.2210/pdb2wm9/pdb
• Related: 1A4R 1AJE 1AM4 1AN0 1CEE 1CF4 1DOA 1E0A 1EES 1GRN 1GZS 1KI1 1KZ7 1KZG 1NF3 1WG7 2ASE 2DFK 2NGR 2WMN 2WMO
• Descriptor: DEDICATOR OF CYTOKINESIS PROTEIN 9, CELL DIVISION CONTROL PROTEIN 42 HOMOLOG, GLYCEROL, ... (4 entities in total)
• Functional Keywords: polymorphism, cell membrane, phosphoprotein, nucleotide-binding, alternative splicing, guanine-nucleotide releasing factor, cell cycle, methylation, lipoprotein, coiled coil, gtp-binding, gefs, dock9, cdc42, prenylation
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 71479.96

Authors

Yang, J.,Roe, S.M.,Barford, D. (deposition date: 2009-06-30, release date: 2009-09-22, Last modification date: 2024-05-08)

Primary citation

Yang, J.,Zhang, Z.,Roe, S.M.,Marshall, C.J.,Barford, D.
Activation of Rho Gtpases by Dock Exchange Factors is Mediated by a Nucleotide Sensor.
Science, 325:1398-, 2009

PubMed Abstract: Activation of Rho guanosine triphosphatases (GTPases) to the guanine triphosphate (GTP)-bound state is a critical event in their regulation of the cytoskeleton and cell signaling. Members of the DOCK family of guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, but the mechanism of activation by their catalytic DHR2 domain is unknown. Through structural analysis of DOCK9-Cdc42 complexes, we identify a nucleotide sensor within the alpha10 helix of the DHR2 domain that contributes to release of guanine diphosphate (GDP) and then to discharge of the activated GTP-bound Cdc42. Magnesium exclusion, a critical factor in promoting GDP release, is mediated by a conserved valine residue within this sensor, whereas binding of GTP-Mg2+ to the nucleotide-free complex results in magnesium-inducing displacement of the sensor to stimulate discharge of Cdc42-GTP. These studies identify an unusual mechanism of GDP release and define the complete GEF catalytic cycle from GDP dissociation followed by GTP binding and discharge of the activated GTPase.

PubMed: 19745154
DOI: 10.1126/SCIENCE.1174468

Experimental method

X-RAY DIFFRACTION (2.2 Å)