4uwx
From Proteopedia
Structure of liprin-alpha3 in complex with mDia1 Diaphanous- inhibitory domain
Structural highlights
Function[DIAP1_MOUSE] Acts in a Rho-dependent manner to recruit PFY1 to the membrane. Required for the assembly of F-actin structures, such as actin cables and stress fibers. Nucleates actin filaments. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Has neurite outgrowth promoting activity. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity).[1] [2] [3] [4] [LIPA3_MOUSE] May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates (By similarity). Publication Abstract from PubMedDiaphanous-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). While the activation of formins by Rho-proteins is well characterized, its inactivation is only marginally understood. Recently, liprin-alpha3 was shown to interact with mDia1. Overexpression of liprin-alpha3 resulted in a reduction of the cellular actin-filament content. The molecular mechanisms how liprin-alpha3 exerts this effect and counteracts mDia1 activation by RhoA are unknown. Here, we functionally and structurally define a minimal liprin-alpha3-core region (LCR), sufficient to recapitulate the liprin-alpha3 determined mDia1-respective cellular functions. We show that liprin-alpha3 alters the interaction-kinetics and -thermodynamics of mDiaN with RhoA-GTP and DAD. RhoA displaces liprin-alpha3 allosterically, whereas DAD competes with liprin-alpha3 for a highly overlapping binding site on mDiaN. liprin-alpha3 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 in mDiaN regulation by liprin-alpha3. Structural and biochemical basis for the inhibitory effect of liprin-alpha3 on mouse Diaphanous 1 (mDia1) function.,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 J Biol Chem. 2015 Apr 24. pii: jbc.M114.621946. PMID:25911102[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Artz, O | Baldus, L | Baumann, U | Boor, S de | Brenig, J | Knyphausen, P | Kuhlmann, N | Lammers, M | Neundorf, I | Scislowski, L | Trauschies, P | Wroblowski, S | Actin polymerisation | Actin-nucleation factor - diaphanous-related formin | Cell motility | Fh1 | Fh2 domain | Peptide-binding protein | Rhognbp | Synape maturation
