| Structural highlights
Function
[DIAP1_MOUSE] Acts in a Rho-dependent manner to recruit PFY1 to the membrane. Required for the assembly of F-actin structures, such as actin cables and stress fibers. Nucleates actin filaments. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Has neurite outgrowth promoting activity. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity).[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Formins induce the nucleation and polymerisation of unbranched actin filaments via the formin-homology domains 1 and 2. Diaphanous-related formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the amino-terminal (N-terminal) region and a carboxy-terminal Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an autoinhibited inactive conformation. Binding of active Rho releases DAD and activates the catalytic activity of mDia. Here, we report on the interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and its release by Rho*GTP. We have defined the elements required for tight binding and solved the three-dimensional structure of a complex between an mDia(N) construct and DAD by X-ray crystallography. The core DAD region is an alpha-helical peptide, which binds in the most highly conserved region of mDia(N) using mainly hydrophobic interactions. The structure suggests a two-step mechanism for release of autoinhibition whereby Rho*GTP, although having a partially nonoverlapping binding site, displaces DAD by ionic repulsion and steric clashes. We show that Rho*GTP accelerates the dissociation of DAD from the mDia(N)*DAD complex.
The regulation of mDia1 by autoinhibition and its release by Rho*GTP.,Lammers M, Rose R, Scrima A, Wittinghofer A EMBO J. 2005 Dec 7;24(23):4176-87. Epub 2005 Nov 17. PMID:16292343[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J. 1997 Jun 2;16(11):3044-56. PMID:9214622 doi:http://dx.doi.org/10.1093/emboj/16.11.3044
- ↑ Tominaga T, Sahai E, Chardin P, McCormick F, Courtneidge SA, Alberts AS. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol Cell. 2000 Jan;5(1):13-25. PMID:10678165
- ↑ Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y, Narumiya S, Watanabe N. Actin polymerization-driven molecular movement of mDia1 in living cells. Science. 2004 Mar 26;303(5666):2007-10. PMID:15044801 doi:http://dx.doi.org/10.1126/science.1093923
- ↑ Schwaibold EM, Brandt DT. Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1. Biochem Biophys Res Commun. 2008 Aug 29;373(3):366-72. doi:, 10.1016/j.bbrc.2008.06.042. Epub 2008 Jun 20. PMID:18572016 doi:http://dx.doi.org/10.1016/j.bbrc.2008.06.042
- ↑ Lammers M, Rose R, Scrima A, Wittinghofer A. The regulation of mDia1 by autoinhibition and its release by Rho*GTP. EMBO J. 2005 Dec 7;24(23):4176-87. Epub 2005 Nov 17. PMID:16292343
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