Function of the N-terminus of zizimin1

Autoinhibition and membrane targeting

Nahum Meller, M. Jody Westbrook, John D. Shannon, Chittibabu Guda, Martin A. Schwartz

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Rho family small GTPases are critical regulators of multiple cellular functions. Dbl-homology-domain-containing proteins are the classical GEFs (guanine nucleotide exchange factors) responsible for activation of Rho proteins. Zizimin1 is a Cdc42-specific GEF that belongs to a second family of mammalian Rho-GEFs, CZH [CDM (Ced-5/DOCK180/Myoblast city)-zizimin homology] proteins, which possess a novel type of GEF domain. CZH proteins can be divided into a subfamily related to DOCK 180 and a subfamily related to ziziminl. The two groups share two conserved regions named the CZH1 (or DHR1) domain and the CZH2 (DHR2 or DOCKER) domains, the latter exhibiting GEF activity. We now show that limited proteolysis of zizimin1 suggests the existence of structural domains that do not correspond to those identified on the basis of homologies. We demonstrate that the N-terminal half binds to the GEF domain through three distinct areas, including the CZH1, to inhibit the interaction with Cdc42. The N-terminal PH (pleckstrin homology) domain binds phosphoinositides and mediates zizimin1 membrane targeting. These results define two novel functions for the N-terminal region of zizimin1.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalBiochemical Journal
Volume409
Issue number2
DOIs
StatePublished - Jan 15 2008

Fingerprint

Guanine Nucleotide Exchange Factors
Membranes
Myoblasts
Proteins
Rho Guanine Nucleotide Exchange Factors
Proteolysis
Monomeric GTP-Binding Proteins
Phosphatidylinositols
Chemical activation

Keywords

  • DOCK11
  • DOCK9
  • Limited proteolysis
  • Protein structure
  • Zizimin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Function of the N-terminus of zizimin1 : Autoinhibition and membrane targeting. / Meller, Nahum; Westbrook, M. Jody; Shannon, John D.; Guda, Chittibabu; Schwartz, Martin A.

In: Biochemical Journal, Vol. 409, No. 2, 15.01.2008, p. 525-533.

Research output: Contribution to journalArticle

Meller, N, Westbrook, MJ, Shannon, JD, Guda, C & Schwartz, MA 2008, 'Function of the N-terminus of zizimin1: Autoinhibition and membrane targeting', Biochemical Journal, vol. 409, no. 2, pp. 525-533. https://doi.org/10.1042/BJ20071263
Meller, Nahum ; Westbrook, M. Jody ; Shannon, John D. ; Guda, Chittibabu ; Schwartz, Martin A. / Function of the N-terminus of zizimin1 : Autoinhibition and membrane targeting. In: Biochemical Journal. 2008 ; Vol. 409, No. 2. pp. 525-533.
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