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| | ==NMR structure of human cofilin== | | ==NMR structure of human cofilin== |
| - | <StructureSection load='1q8x' size='340' side='right'caption='[[1q8x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1q8x' size='340' side='right'caption='[[1q8x]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1q8x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q8X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q8x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q8X FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1q8g|1q8g]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CFL1 OR CFL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q8x OCA], [https://pdbe.org/1q8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q8x RCSB], [https://www.ebi.ac.uk/pdbsum/1q8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q8x 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=1q8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q8x OCA], [https://pdbe.org/1q8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q8x RCSB], [https://www.ebi.ac.uk/pdbsum/1q8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q8x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/COF1_HUMAN COF1_HUMAN]] Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:15580268</ref> <ref>PMID:21834987</ref>
| + | [https://www.uniprot.org/uniprot/COF1_HUMAN COF1_HUMAN] Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:15580268</ref> <ref>PMID:21834987</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ball, L J]] | + | [[Category: Ball LJ]] |
| - | [[Category: Kuhne, R]] | + | [[Category: Kuhne R]] |
| - | [[Category: Pope, B J]] | + | [[Category: Pope BJ]] |
| - | [[Category: Weeds, A G]] | + | [[Category: Weeds AG]] |
| - | [[Category: Zierler-Gould, K M]] | + | [[Category: Zierler-Gould KM]] |
| - | [[Category: Actin cytoskeleton]]
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| - | [[Category: Adf/cofilin]]
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| - | [[Category: Chemical shift perturbation]]
| + | |
| - | [[Category: G-actin binding]]
| + | |
| - | [[Category: Structural protein]]
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| Structural highlights
Function
COF1_HUMAN Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization.[1] [2]
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
Human actin-depolymerizing factor (ADF) and cofilin are pH-sensitive, actin-depolymerizing proteins. Although 72% identical in sequence, ADF has a much higher depolymerizing activity than cofilin at pH 8. To understand this, we solved the structure of human cofilin using nuclear magnetic resonance and compared it with human ADF. Important sequence differences between vertebrate ADF/cofilins were correlated with unique structural determinants in the F-actin-binding site to account for differences in biochemical activities of the two proteins. Cofilin has a short beta-strand at the C terminus, not found in ADF, which packs against strands beta3/beta4, changing the environment around Lys96, a residue essential for F-actin binding. A salt bridge involving His133 and Asp98 (Glu98 in ADF) may explain the pH sensitivity of human cofilin and ADF; these two residues are fully conserved in vertebrate ADF/cofilins. Chemical shift perturbations identified residues that (i) differ in their chemical environments between wild type cofilin and mutants S3D, which has greatly reduced G-actin binding, and K96Q, which does not bind F-actin; (ii) are affected when G-actin binds cofilin; and (iii) are affected by pH change from 6 to 8. Many residues affected by G-actin binding also show perturbation in the mutants or in response to pH. Our evidence suggests the involvement of residues 133-138 of strand beta5 in all of the activities examined. Because residues in beta5 are perturbed by mutations that affect both G-actin and F-actin binding, this strand forms a "boundary" or "bridge" between the proposed F- and G-actin-binding sites.
Solution structure of human cofilin: actin binding, pH sensitivity, and relationship to actin-depolymerizing factor.,Pope BJ, Zierler-Gould KM, Kuhne R, Weeds AG, Ball LJ J Biol Chem. 2004 Feb 6;279(6):4840-8. Epub 2003 Nov 18. PMID:14627701[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gohla A, Birkenfeld J, Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005 Jan;7(1):21-9. Epub 2004 Dec 5. PMID:15580268 doi:10.1038/ncb1201
- ↑ Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54
- ↑ Pope BJ, Zierler-Gould KM, Kuhne R, Weeds AG, Ball LJ. Solution structure of human cofilin: actin binding, pH sensitivity, and relationship to actin-depolymerizing factor. J Biol Chem. 2004 Feb 6;279(6):4840-8. Epub 2003 Nov 18. PMID:14627701 doi:10.1074/jbc.M310148200
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