|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of the core FH2 domain of mouse mDia1== | | ==Crystal structure of the core FH2 domain of mouse mDia1== |
| - | <StructureSection load='1v9d' size='340' side='right' caption='[[1v9d]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='1v9d' size='340' side='right'caption='[[1v9d]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1v9d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V9D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1V9D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1v9d]] 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=1V9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V9D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.6Å</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=1v9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v9d OCA], [http://pdbe.org/1v9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1v9d RCSB], [http://www.ebi.ac.uk/pdbsum/1v9d PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1v9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v9d OCA], [https://pdbe.org/1v9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v9d RCSB], [https://www.ebi.ac.uk/pdbsum/1v9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v9d 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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v9/1v9d_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v9/1v9d_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| Line 31: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Bugyi, B]] | + | [[Category: Mus musculus]] |
| - | [[Category: Geeves, M A]] | + | [[Category: Bugyi B]] |
| - | [[Category: Kuhlmann, D]] | + | [[Category: Geeves MA]] |
| - | [[Category: Narumiya, S]] | + | [[Category: Kuhlmann D]] |
| - | [[Category: Nyitrai, M]] | + | [[Category: Narumiya S]] |
| - | [[Category: Shimada, A]] | + | [[Category: Nyitrai M]] |
| - | [[Category: Vetter, I R]] | + | [[Category: Shimada A]] |
| - | [[Category: Wittinghofer, A]] | + | [[Category: Vetter IR]] |
| - | [[Category: Helix bundle]]
| + | [[Category: Wittinghofer A]] |
| - | [[Category: Protein binding]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Diaphanous-related formins (Drf) are activated by Rho GTP binding proteins and induce polymerization of unbranched actin filaments. They contain three formin homology domains. Evidence as to the effect of formins on actin polymerization were obtained using FH2/FH1 constructs of various length from different Drfs. Here we define the core FH2 domain as a proteolytically stable domain of approximately 338 residues. The monomeric FH2 domains from mDia1 and mDia3 inhibit polymerization of actin and can bind in a 1:1 complex with F-actin at micromolar concentrations. The X-ray structure analysis of the domain shows an elongated, crescent-shaped molecule consisting of three helical subdomains. The most highly conserved regions of the domain span a distance of 75 A and are both required for barbed-end inhibition. A construct containing an additional 72 residue linker has dramatically different properties: It oligomerizes and induces actin polymerization at subnanomolar concentration.
The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization.,Shimada A, Nyitrai M, Vetter IR, Kuhlmann D, Bugyi B, Narumiya S, Geeves MA, Wittinghofer A Mol Cell. 2004 Feb 27;13(4):511-22. PMID:14992721[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
- ↑ Shimada A, Nyitrai M, Vetter IR, Kuhlmann D, Bugyi B, Narumiya S, Geeves MA, Wittinghofer A. The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization. Mol Cell. 2004 Feb 27;13(4):511-22. PMID:14992721
|
