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:
CreatorsEmailORCIDORCID Put Code
Brenig, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Boor, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knyphausen, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhlmann, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wroblowski, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldus, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scislowski, LukasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artz, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trauschies, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neundorf, InesUNSPECIFIEDorcid.org/0000-0001-6450-3991UNSPECIFIED
Lammers, MichaelUNSPECIFIEDorcid.org/0000-0003-4168-4640UNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FORMIN HOMOLOGY-2 DOMAIN; ACTIN-FILAMENT ELONGATION; LIPRIN-ALPHA PROTEINS; AUTOREGULATORY DOMAIN; STRUCTURE VALIDATION; INDUCED NUCLEATION; CRYSTAL-STRUCTURES; COILED COILS; FH1 DOMAIN; BINDINGMultiple languages
Biochemistry & Molecular BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40124

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