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 journalArticle

108 Citations (Scopus)

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 1998

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Mutagenesis
GTP Phosphohydrolases
Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins
Proteins
Guanosine Triphosphate
Ligands
platelet protein P47

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • 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

Structure and mutagenesis of the Dbl homology domain. / Aghazadeh, Behzad; Zhu, Kejin; Kubiseski, Terrance J.; Liu, Grace A.; Pawson, Tony; Zheng, Yi; Rosen, Michael K.

In: Nature Structural Biology, Vol. 5, No. 12, 12.1998, p. 1098-1107.

Research output: Contribution to journalArticle

Aghazadeh, B, Zhu, K, Kubiseski, TJ, Liu, GA, Pawson, T, Zheng, Y & Rosen, MK 1998, 'Structure and mutagenesis of the Dbl homology domain', Nature Structural Biology, vol. 5, no. 12, pp. 1098-1107. https://doi.org/10.1038/4209
Aghazadeh B, Zhu K, Kubiseski TJ, Liu GA, Pawson T, Zheng Y et al. Structure and mutagenesis of the Dbl homology domain. Nature Structural Biology. 1998 Dec;5(12):1098-1107. https://doi.org/10.1038/4209
Aghazadeh, Behzad ; Zhu, Kejin ; Kubiseski, Terrance J. ; Liu, Grace A. ; Pawson, Tony ; Zheng, Yi ; Rosen, Michael K. / Structure and mutagenesis of the Dbl homology domain. In: Nature Structural Biology. 1998 ; Vol. 5, No. 12. pp. 1098-1107.
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