6AJL

DOCK7 mutant I1836Y complexed with Cdc42

Summary for 6AJL

• Entry DOI: 10.2210/pdb6ajl/pdb
• Related: 6AJ4
• Descriptor: Dedicator of cytokinesis protein 7, Cell division control protein 42 homolog (2 entities in total)
• Functional Keywords: dock, gef, dhr-2, gtpase, rho, rac, cdc42, mutant, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 221556.51

Authors

Kukimoto-Niino, M.,Shirouzu, M. (deposition date: 2018-08-28, release date: 2019-03-20, Last modification date: 2023-11-22)

Primary citation

Kukimoto-Niino, M.,Tsuda, K.,Ihara, K.,Mishima-Tsumagari, C.,Honda, K.,Ohsawa, N.,Shirouzu, M.
Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor.
Structure, 27:741-, 2019

PubMed Abstract: The Dedicator Of CytoKinesis (DOCK) family of atypical guanine nucleotide exchange factors activates the Rho family GTPases Rac and/or Cdc42 through DOCK homology region 2 (DHR-2). Previous structural analyses of the DHR-2 domains of DOCK2 and DOCK9 have shown that they preferentially bind Rac1 and Cdc42, respectively; however, the molecular mechanism by which DHR-2 distinguishes between these GTPases is unclear. Here we report the crystal structure of the Cdc42-bound form of the DOCK7 DHR-2 domain showing dual specificity for Rac1 and Cdc42. The structure revealed increased substrate tolerance of DOCK7 at the interfaces with switch 1 and residue 56 of Cdc42. Furthermore, molecular dynamics simulations showed a closed-to-open conformational change in the DOCK7 DHR-2 domain between the Cdc42- and Rac1-bound states by lobe B displacement. Our results suggest that lobe B acts as a sensor for identifying different switch 1 conformations and explain how DOCK7 recognizes both Rac1 and Cdc42.

PubMed: 30853411
DOI: 10.1016/j.str.2019.02.001

Experimental method

X-RAY DIFFRACTION (3.23 Å)