Structural and Biochemical Basis for the Inhibitory Effect of Liprin-α3 on Mouse Diaphanous 1 (mDia1) Function.

Autor:	Brenig J; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., de Boor S; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Knyphausen P; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Kuhlmann N; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Wroblowski S; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Baldus L; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Scislowski L; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Artz O; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Trauschies P; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and., Baumann U; the Institute for Biochemistry, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany., Neundorf I; the Institute for Biochemistry, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany., Lammers M; From the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Joseph-Stelzmann-Strasse 26, University of Cologne, 50931 Cologne, Germany and michael.lammers@uni-koeln.de.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Jun 05; Vol. 290 (23), pp. 14314-27. Date of Electronic Publication: 2015 Apr 24.
DOI:	10.1074/jbc.M114.621946
Abstrakt:	Diaphanous-related formins are eukaryotic actin nucleation factors regulated by an autoinhibitory interaction between the N-terminal RhoGTPase-binding domain (mDiaN) and the C-terminal Diaphanous-autoregulatory domain (DAD). Although the activation of formins by Rho proteins is well characterized, its inactivation is only marginally understood. Recently, liprin-α3 was shown to interact with mDia1. Overexpression of liprin-α3 resulted in a reduction of the cellular actin filament content. The molecular mechanisms of how liprin-α3 exerts this effect and counteracts mDia1 activation by RhoA are unknown. Here, we functionally and structurally define a minimal liprin-α3 core region, sufficient to recapitulate the liprin-α3 determined mDia1-respective cellular functions. We show that liprin-α3 alters the interaction kinetics and thermodynamics of mDiaN with RhoA·GTP and DAD. RhoA displaces liprin-α3 allosterically, whereas DAD competes with liprin-α3 for a highly overlapping binding site on mDiaN. Liprin-α3 regulates actin polymerization by lowering the regulatory potency of RhoA and DAD on mDiaN. We present a model of a mechanistically unexplored and new aspect of mDiaN regulation by liprin-α3. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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