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| | <StructureSection load='3p53' size='340' side='right'caption='[[3p53]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3p53' size='340' side='right'caption='[[3p53]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p53]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P53 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P53 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p53]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P53 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P53 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAN1, FSCN1, HSN, Human, SNL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</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=3p53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p53 OCA], [https://pdbe.org/3p53 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p53 RCSB], [https://www.ebi.ac.uk/pdbsum/3p53 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p53 ProSAT]</span></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=3p53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p53 OCA], [https://pdbe.org/3p53 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p53 RCSB], [https://www.ebi.ac.uk/pdbsum/3p53 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p53 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FSCN1_HUMAN FSCN1_HUMAN]] Organizes filamentous actin into bundles with a minimum of 4.1:1 actin/fascin ratio. Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration.<ref>PMID:9362073</ref> <ref>PMID:9571235</ref> <ref>PMID:20137952</ref> <ref>PMID:20393565</ref>
| + | [https://www.uniprot.org/uniprot/FSCN1_HUMAN FSCN1_HUMAN] Organizes filamentous actin into bundles with a minimum of 4.1:1 actin/fascin ratio. Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration.<ref>PMID:9362073</ref> <ref>PMID:9571235</ref> <ref>PMID:20137952</ref> <ref>PMID:20393565</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Fascin is the main actin filament bundling protein in filopodia. Because of the important role filopodia play in cell migration, fascin is emerging as a major target for cancer drug discovery. However, an understanding of the mechanism of bundle formation by fascin is critically lacking. Fascin consists of four beta-trefoil domains. Here, we show that fascin contains two major actin-binding sites, coinciding with regions of high sequence conservation in beta-trefoil domains 1 and 3. The site in beta-trefoil-1 is located near the binding site of the fascin inhibitor macroketone and comprises residue Ser-39, whose phosphorylation by protein kinase C down-regulates actin bundling and formation of filopodia. The site in beta-trefoil-3 is related by pseudo-2-fold symmetry to that in beta-trefoil-1. The two sites are approximately 5 nm apart, resulting in a distance between actin filaments in the bundle of approximately 8.1 nm. Residue mutations in both sites disrupt bundle formation in vitro as assessed by co-sedimentation with actin and electron microscopy and severely impair formation of filopodia in cells as determined by rescue experiments in fascin-depleted cells. Mutations of other areas of the fascin surface also affect actin bundling and formation of filopodia albeit to a lesser extent, suggesting that, in addition to the two major actin-binding sites, fascin makes secondary contacts with other filaments in the bundle. In a high resolution crystal structure of fascin, molecules of glycerol and polyethylene glycol are bound in pockets located within the two major actin-binding sites. These molecules could guide the rational design of new anticancer fascin inhibitors.
| + | |
| - | | + | |
| - | Mechanism of actin filament bundling by fascin.,Jansen S, Collins A, Yang C, Rebowski G, Svitkina T, Dominguez R J Biol Chem. 2011 Aug 26;286(34):30087-96. Epub 2011 Jun 18. PMID:21685497<ref>PMID:21685497</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3p53" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dominguez, R]] | + | [[Category: Dominguez R]] |
| - | [[Category: Jansen, S]] | + | [[Category: Jansen S]] |
| - | [[Category: Beta-trefoil domain]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
FSCN1_HUMAN Organizes filamentous actin into bundles with a minimum of 4.1:1 actin/fascin ratio. Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration.[1] [2] [3] [4]
See Also
References
- ↑ Adams JC. Characterization of cell-matrix adhesion requirements for the formation of fascin microspikes. Mol Biol Cell. 1997 Nov;8(11):2345-63. PMID:9362073
- ↑ Yamashiro S, Yamakita Y, Ono S, Matsumura F. Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility of epithelial cells. Mol Biol Cell. 1998 May;9(5):993-1006. PMID:9571235
- ↑ Li A, Dawson JC, Forero-Vargas M, Spence HJ, Yu X, Konig I, Anderson K, Machesky LM. The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol. 2010 Feb 23;20(4):339-45. doi: 10.1016/j.cub.2009.12.035. Epub 2010, Feb 4. PMID:20137952 doi:10.1016/j.cub.2009.12.035
- ↑ Chen L, Yang S, Jakoncic J, Zhang JJ, Huang XY. Migrastatin analogues target fascin to block tumour metastasis. Nature. 2010 Apr 15;464(7291):1062-6. PMID:20393565 doi:10.1038/nature08978
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