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| | ==Structure of liprin-alpha3 in complex with mDia1 Diaphanous- inhibitory domain== | | ==Structure of liprin-alpha3 in complex with mDia1 Diaphanous- inhibitory domain== |
| - | <StructureSection load='4uwx' size='340' side='right' caption='[[4uwx]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='4uwx' size='340' side='right'caption='[[4uwx]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uwx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UWX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uwx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UWX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=144:TRIS-HYDROXYMETHYL-METHYL-AMMONIUM'>144</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwx OCA], [http://pdbe.org/4uwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uwx RCSB], [http://www.ebi.ac.uk/pdbsum/4uwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwx ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=144:TRIS-HYDROXYMETHYL-METHYL-AMMONIUM'>144</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4uwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwx OCA], [https://pdbe.org/4uwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uwx RCSB], [https://www.ebi.ac.uk/pdbsum/4uwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DIAP1_MOUSE 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).<ref>PMID:9214622</ref> <ref>PMID:10678165</ref> <ref>PMID:15044801</ref> <ref>PMID:18572016</ref> [[http://www.uniprot.org/uniprot/LIPA3_MOUSE 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). | + | [https://www.uniprot.org/uniprot/DIAP1_MOUSE 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).<ref>PMID:9214622</ref> <ref>PMID:10678165</ref> <ref>PMID:15044801</ref> <ref>PMID:18572016</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Artz, O]] | + | [[Category: Large Structures]] |
| - | [[Category: Baldus, L]] | + | [[Category: Mus musculus]] |
| - | [[Category: Baumann, U]] | + | [[Category: Artz O]] |
| - | [[Category: Boor, S de]] | + | [[Category: Baldus L]] |
| - | [[Category: Brenig, J]] | + | [[Category: Baumann U]] |
| - | [[Category: Knyphausen, P]] | + | [[Category: Brenig J]] |
| - | [[Category: Kuhlmann, N]] | + | [[Category: Knyphausen P]] |
| - | [[Category: Lammers, M]] | + | [[Category: Kuhlmann N]] |
| - | [[Category: Neundorf, I]] | + | [[Category: Lammers M]] |
| - | [[Category: Scislowski, L]] | + | [[Category: Neundorf I]] |
| - | [[Category: Trauschies, P]] | + | [[Category: Scislowski L]] |
| - | [[Category: Wroblowski, S]] | + | [[Category: Trauschies P]] |
| - | [[Category: Actin polymerisation]] | + | [[Category: Wroblowski S]] |
| - | [[Category: Actin-nucleation factor - diaphanous-related formin]]
| + | [[Category: De Boor S]] |
| - | [[Category: Cell motility]]
| + | |
| - | [[Category: Fh1]]
| + | |
| - | [[Category: Fh2 domain]]
| + | |
| - | [[Category: Peptide-binding protein]]
| + | |
| - | [[Category: Rhognbp]]
| + | |
| - | [[Category: Synape maturation]]
| + | |
| 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]
Publication Abstract from PubMed
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). 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
- ↑ Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J. 1997 Jun 2;16(11):3044-56. PMID:9214622 doi:http://dx.doi.org/10.1093/emboj/16.11.3044
- ↑ Tominaga T, Sahai E, Chardin P, McCormick F, Courtneidge SA, Alberts AS. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol Cell. 2000 Jan;5(1):13-25. PMID:10678165
- ↑ Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y, Narumiya S, Watanabe N. Actin polymerization-driven molecular movement of mDia1 in living cells. Science. 2004 Mar 26;303(5666):2007-10. PMID:15044801 doi:http://dx.doi.org/10.1126/science.1093923
- ↑ Schwaibold EM, Brandt DT. Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1. Biochem Biophys Res Commun. 2008 Aug 29;373(3):366-72. doi:, 10.1016/j.bbrc.2008.06.042. Epub 2008 Jun 20. PMID:18572016 doi:http://dx.doi.org/10.1016/j.bbrc.2008.06.042
- ↑ 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. 2015 Apr 24. pii: jbc.M114.621946. PMID:25911102 doi:http://dx.doi.org/10.1074/jbc.M114.621946
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