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| | ==The crystal structure of human fascin 1 K358A mutant== | | ==The crystal structure of human fascin 1 K358A mutant== |
| - | <StructureSection load='4gp3' size='340' side='right' caption='[[4gp3]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4gp3' size='340' side='right'caption='[[4gp3]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gp3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GP3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gp3]] 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=4GP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GP3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gp0|4gp0]], [[4gov|4gov]], [[4goy|4goy]]</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=4gp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gp3 OCA], [https://pdbe.org/4gp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gp3 RCSB], [https://www.ebi.ac.uk/pdbsum/4gp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gp3 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAN1, FSCN1, HSN, SNL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4gp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gp3 OCA], [http://pdbe.org/4gp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gp3 RCSB], [http://www.ebi.ac.uk/pdbsum/4gp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gp3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4gp3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4gp3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Fascin|Fascin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, S]] | + | [[Category: Chen L]] |
| - | [[Category: Diaz-Avalos, R]] | + | [[Category: Chen S]] |
| - | [[Category: Huang, F K]] | + | [[Category: Diaz-Avalos R]] |
| - | [[Category: Huang, J]] | + | [[Category: Huang FK]] |
| - | [[Category: Huang, X Y]] | + | [[Category: Huang J]] |
| - | [[Category: Jakoncic, J]] | + | [[Category: Huang XY]] |
| - | [[Category: Leo-Macias, A]] | + | [[Category: Jakoncic J]] |
| - | [[Category: Yang, S Y]] | + | [[Category: Leo-Macias A]] |
| - | [[Category: Zhang, J J]] | + | [[Category: Yang SY]] |
| - | [[Category: Actin]]
| + | [[Category: Zhang JJ]] |
| - | [[Category: Actin bundling protein]]
| + | |
| - | [[Category: Actin-binding]]
| + | |
| - | [[Category: Beta-trefoil]]
| + | |
| - | [[Category: Cancer]]
| + | |
| - | [[Category: Cell migration]]
| + | |
| - | [[Category: Metastasis]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| 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]
Publication Abstract from PubMed
Filopodia are cell surface protrusions that are essential for cell migration. This finger-like structure is supported by rigid tightly-bundled actin filaments. The protein responsible for actin-bundling in filopodia is fascin. However the mechanism by which fascin functions in filopodial formation is not clear. Here we provide biochemical, cryo-electron tomographic and X-ray crystal structural data demonstrating the unique structural characteristics of fascin. Systematic mutagenesis studies on 100 mutants of fascin indicate that there are two major actin-binding sites on fascin. Crystal structures of four fascin mutants reveal concerted conformational changes in fascin from inactive to active states in the process of actin bundling. Mutations in any one of the actin-binding sites impair the cellular function of fascin in filopodial formation. Altogether, our data reveal the molecular mechanism of fascin function in filopodial formation.
Molecular Mechanism of Fascin Function in Filopodial Formation.,Yang S, Huang FK, Huang J, Chen S, Jakoncic J, Leo-Macias A, Diaz-Avalos R, Chen L, Zhang JJ, Huang XY J Biol Chem. 2012 Nov 26. PMID:23184945[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Yang S, Huang FK, Huang J, Chen S, Jakoncic J, Leo-Macias A, Diaz-Avalos R, Chen L, Zhang JJ, Huang XY. Molecular Mechanism of Fascin Function in Filopodial Formation. J Biol Chem. 2012 Nov 26. PMID:23184945 doi:http://dx.doi.org/10.1074/jbc.M112.427971
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