4UWX

Structure of liprin-alpha3 in complex with mDia1 Diaphanous- inhibitory domain

Summary for 4UWX

• Entry DOI: 10.2210/pdb4uwx/pdb
• Descriptor: PROTEIN DIAPHANOUS HOMOLOG 1, LIPRIN-ALPHA-3, NICKEL (II) ION, ... (5 entities in total)
• Functional Keywords: peptide-binding protein, actin polymerisation, rhognbps, synape maturation, cell motility, fh1, fh2 domain, actin-nucleation factor - diaphanous-related formin, peptide binding protein
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Cellular location: Cell membrane : O08808; Cytoplasm : P60469
• Total number of polymer chains: 4
• Total formula weight: 59215.46

Authors

Brenig, J.,de Boor, S.,Knyphausen, P.,Kuhlmann, N.,Wroblowski, S.,Baldus, L.,Scislowski, L.,Artz, O.,Trauschies, P.,Baumann, U.,Neundorf, I.,Lammers, M. (deposition date: 2014-08-15, release date: 2015-05-06, Last modification date: 2024-01-10)

Primary citation

Brenig, J.,De Boor, S.,Knyphausen, P.,Kuhlmann, N.,Wroblowski, S.,Baldus, L.,Scislowski, L.,Artz, O.,Trauschies, P.,Baumann, U.,Neundorf, I.,Lammers, M.
Structural and Biochemical Basis for the Inhibitory Effect of Liprin-Alpha3 on Mouse Diaphanous 1 (Mdia1) Function.
J.Biol.Chem., 290:14314-, 2015

PubMed Abstract: 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.

PubMed: 25911102
DOI: 10.1074/JBC.M114.621946

Experimental method

X-RAY DIFFRACTION (1.65 Å)