4UWX

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

4UWX の概要

• エントリーDOI: 10.2210/pdb4uwx/pdb
• 分子名称: PROTEIN DIAPHANOUS HOMOLOG 1, LIPRIN-ALPHA-3, NICKEL (II) ION, ... (5 entities in total)
• 機能のキーワード: peptide-binding protein, actin polymerisation, rhognbps, synape maturation, cell motility, fh1, fh2 domain, actin-nucleation factor - diaphanous-related formin, peptide binding protein
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• 細胞内の位置: Cell membrane : O08808; Cytoplasm : P60469
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59215.46

構造登録者

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. (登録日: 2014-08-15, 公開日: 2015-05-06, 最終更新日: 2024-01-10)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.65 Å)