8I5W

Crystal structure of the DHR-2 domain of DOCK10 in complex with Rac1

Summary for 8I5W

• Entry DOI: 10.2210/pdb8i5w/pdb
• Related: 8I5F 8I5V
• Descriptor: Dedicator of cytokinesis protein 10, Ras-related C3 botulinum toxin substrate 1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: dock, gef, dhr-2, gtpase, rho, rac, cdc42, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 52930.22

Authors

Kukimoto-Niino, M.,Mishima-Tsumagari, C.,Ihara, K.,Fukui, Y.,Yokoyama, S.,Shirouzu, M. (deposition date: 2023-01-26, release date: 2023-03-15, Last modification date: 2024-05-29)

Primary citation

Kukimoto-Niino, M.,Ihara, K.,Mishima-Tsumagari, C.,Inoue, M.,Fukui, Y.,Yokoyama, S.,Shirouzu, M.
Structural basis for the dual GTPase specificity of the DOCK10 guanine nucleotide exchange factor.
Biochem.Biophys.Res.Commun., 653:12-20, 2023

PubMed Abstract: Dedicator of cytokinesis 10 (DOCK10), an evolutionarily conserved guanine nucleotide exchange factor (GEF) for Rho GTPases, has the unique specificity within the DOCK-D subfamily to activate both Cdc42 and Rac, but the structural bases for these activities remained unknown. Here we present the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1. The structures revealed that DOCK10 binds to Cdc42 or Rac1 by slightly changing the arrangement of its two catalytic lobes. DOCK10 also has a flexible binding pocket for the 56th GTPase residue, allowing a novel interaction with Trp56. The conserved residues in switch 1 of Cdc42 and Rac1 showed common interactions with the unique Lys-His sequence in the β5/β6 loop of DOCK10. However, the interaction of switch 1 in Rac1 was less stable than that of switch 1 in Cdc42, due to amino acid differences at positions 27 and 30. Structure-based mutagenesis identified the DOCK10 residues that determine the Cdc42/Rac1 dual specificity.

PubMed: 36848820
DOI: 10.1016/j.bbrc.2023.02.054

Experimental method

X-RAY DIFFRACTION (2.432 Å)