Universität zu Köln

Brenig, Julian, de Boor, Susanne, Knyphausen, Philipp, Kuhlmann, Nora, Wroblowski, Sarah, Baldus, Linda, Scislowski, Lukas, Artz, Oliver, Trauschies, Philip, Baumann, Ulrich, Neundorf, Ines ORCID: 0000-0001-6450-3991 and Lammers, Michael ORCID: 0000-0003-4168-4640 (2015). Structural and Biochemical Basis for the Inhibitory Effect of Liprin-alpha 3 on Mouse Diaphanous 1 (mDia1) Function. J. Biol. Chem., 290 (23). S. 14314 - 14328. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

Diaphanous-related formins are eukaryotic actin nucleation factors regulated by an autoinhibitory interaction between the N-terminal RhoGTPase-binding domain (mDia(N)) 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-alpha 3 was shown to interact with mDia1. Overexpression of liprin-alpha 3 resulted in a reduction of the cellular actin filament content. The molecular mechanisms of how liprin-alpha 3 exerts this effect and counteracts mDia1 activation by RhoA are unknown. Here, we functionally and structurally define a minimal liprin-alpha 3 core region, sufficient to recapitulate the liprin-alpha 3 determined mDia1-respective cellular functions. We show that liprin-alpha 3 alters the interaction kinetics and thermodynamics of mDia(N) with RhoA center dot GTP and DAD. RhoA displaces liprin-alpha 3 allosterically, whereas DAD competes with liprin-alpha 3 for a highly overlapping binding site on mDia(N). Liprin-alpha 3 regulates actin polymerization by lowering the regulatory potency of RhoA and DAD on mDia(N). We present a model of a mechanistically unexplored and new aspect of mDia(N) regulation by liprin-alpha 3.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brenig, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED de Boor, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhlmann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Wroblowski, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Scislowski, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Artz, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Trauschies, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Lammers, Michael UNSPECIFIED orcid.org/0000-0003-4168-4640 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-401240
DOI:	10.1074/jbc.M114.621946
Journal or Publication Title:	J. Biol. Chem.
Volume:	290
Number:	23
Page Range:	S. 14314 - 14328
Date:	2015
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FORMIN HOMOLOGY-2 DOMAIN; ACTIN-FILAMENT ELONGATION; LIPRIN-ALPHA PROTEINS; AUTOREGULATORY DOMAIN; STRUCTURE VALIDATION; INDUCED NUCLEATION; CRYSTAL-STRUCTURES; COILED COILS; FH1 DOMAIN; BINDING Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/40124