2YIN

STRUCTURE OF THE COMPLEX BETWEEN Dock2 AND Rac1.

Summary for 2YIN

• Entry DOI: 10.2210/pdb2yin/pdb
• Related: 1E96 1FOE 1G4U 1HE1 1HH4 1I4D 1I4L 1I4T 1MH1 1RYF 1RYH 2FJU 2VRW 2WKP 2WKQ 2WKR
• Descriptor: DEDICATOR OF CYTOKINESIS PROTEIN 2, RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE 1 (3 entities in total)
• Functional Keywords: apoptosis, dock, dock guanine nucleotide exchange factors, rho gtpase
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 147023.65

Authors

Kulkarni, K.A.,Yang, J.,Zhang, Z.,Barford, D. (deposition date: 2011-05-16, release date: 2011-05-25, Last modification date: 2023-12-20)

Primary citation

Kulkarni, K.,Yang, J.,Zhang, Z.,Barford, D.
Multiple Factors Confer Specific Cdc42 and Rac Protein Activation by Dedicator of Cytokinesis (Dock) Nucleotide Exchange Factors.
J.Biol.Chem., 286:25341-, 2011

PubMed Abstract: DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

PubMed: 21613211
DOI: 10.1074/JBC.M111.236455

Experimental method

X-RAY DIFFRACTION (2.7 Å)