8I5F

Crystal structure of the DHR-2 domain of DOCK10 in complex with Cdc42 (T17N mutant)

8I5F の概要

• エントリーDOI: 10.2210/pdb8i5f/pdb
• 関連するPDBエントリー: 8I5V 8I5W
• 分子名称: Dedicator of cytokinesis protein 10, Cell division control protein 42 homolog (3 entities in total)
• 機能のキーワード: gef, gtpase, rho, cdc42, rac, signaling protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 156928.79

構造登録者

Kukimoto-Niino, M.,Mishima-Tsumagari, C.,Fukui, Y.,Yokoyama, S.,Shirouzu, M. (登録日: 2023-01-25, 公開日: 2023-03-15, 最終更新日: 2024-05-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)