Structure and mutagenesis of the Dbl homology domain

Behzad Aghazadeh, Kejin Zhu, Terrance J. Kubiseski, Grace A. Liu, Tony Pawson, Yi Zheng, Michael K. Rosen

Research output: Contribution to journalReview article

108 Scopus citations

Abstract

Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a ~200 residue catalytic Dbl- homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (βPIX). The domain is composed of 11 α-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH- ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.

Original languageEnglish (US)
Pages (from-to)1098-1107
Number of pages10
JournalNature Structural Biology
Volume5
Issue number12
DOIs
StatePublished - Dec 1 1998

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ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

Cite this

Aghazadeh, B., Zhu, K., Kubiseski, T. J., Liu, G. A., Pawson, T., Zheng, Y., & Rosen, M. K. (1998). Structure and mutagenesis of the Dbl homology domain. Nature Structural Biology, 5(12), 1098-1107. https://doi.org/10.1038/4209