1unc

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of the human villin C-terminal headpiece subdomain

Structural highlights

1unc is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

VILI_HUMAN Note=Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure.

Function

VILI_HUMAN Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13]

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

Headpiece (HP) is a 76-residue F-actin-binding module at the C terminus of many cytoskeletal proteins. Its 35-residue C-terminal subdomain is one of the smallest known motifs capable of autonomously adopting a stable, folded structure in the absence of any disulfide bridges, metal ligands, or unnatural amino acids. We report the three-dimensional solution structures of the C-terminal headpiece subdomains of human villin (HVcHP) and human advillin (HAcHP), determined by two-dimensional 1H-NMR. They represent the second and third structures of such C-terminal headpiece subdomains to be elucidated so far. A comparison with the structure of the chicken villin C-terminal subdomain reveals a high structural conservation. Both C-terminal subdomains bind specifically to F-actin. Mutagenesis is used to demonstrate the involvement of Trp 64 in the F-actin-binding surface. The latter residue is part of a conserved structural feature, in which the surface-exposed indole ring is stacked on the proline and lysine side chain embedded in a PXWK sequence motif. On the basis of the structural and mutational data concerning Trp 64 reported here, the results of a cysteine-scanning mutagenesis study of full headpiece, and a phage display mutational study of the 69-74 fragment, we propose a modification of the model, elaborated by Vardar and coworkers, for the binding of headpiece to F-actin.

Solution structures of the C-terminal headpiece subdomains of human villin and advillin, evaluation of headpiece F-actin-binding requirements.,Vermeulen W, Vanhaesebrouck P, Van Troys M, Verschueren M, Fant F, Goethals M, Ampe C, Martins JC, Borremans FA Protein Sci. 2004 May;13(5):1276-87. PMID:15096633^[14]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Northrop J, Weber A, Mooseker MS, Franzini-Armstrong C, Bishop MF, Dubyak GR, Tucker M, Walsh TP. Different calcium dependence of the capping and cutting activities of villin. J Biol Chem. 1986 Jul 15;261(20):9274-81. PMID:3087992
↑ Zhai L, Zhao P, Panebra A, Guerrerio AL, Khurana S. Tyrosine phosphorylation of villin regulates the organization of the actin cytoskeleton. J Biol Chem. 2001 Sep 28;276(39):36163-7. Epub 2001 Aug 10. PMID:11500485 doi:10.1074/jbc.C100418200
↑ Kumar N, Zhao P, Tomar A, Galea CA, Khurana S. Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the actin cytoskeleton. J Biol Chem. 2004 Jan 23;279(4):3096-110. Epub 2003 Nov 1. PMID:14594952 doi:10.1074/jbc.M308878200
↑ Kumar N, Khurana S. Identification of a functional switch for actin severing by cytoskeletal proteins. J Biol Chem. 2004 Jun 11;279(24):24915-8. Epub 2004 Apr 14. PMID:15084600 doi:10.1074/jbc.C400110200
↑ Kumar N, Tomar A, Parrill AL, Khurana S. Functional dissection and molecular characterization of calcium-sensitive actin-capping and actin-depolymerizing sites in villin. J Biol Chem. 2004 Oct 22;279(43):45036-46. Epub 2004 Jul 21. PMID:15272027 doi:10.1074/jbc.M405424200
↑ Tomar A, Wang Y, Kumar N, George S, Ceacareanu B, Hassid A, Chapman KE, Aryal AM, Waters CM, Khurana S. Regulation of cell motility by tyrosine phosphorylated villin. Mol Biol Cell. 2004 Nov;15(11):4807-17. Epub 2004 Sep 1. PMID:15342783 doi:10.1091/mbc.E04-05-0431
↑ Tomar A, George S, Kansal P, Wang Y, Khurana S. Interaction of phospholipase C-gamma1 with villin regulates epithelial cell migration. J Biol Chem. 2006 Oct 20;281(42):31972-86. Epub 2006 Aug 18. PMID:16921170 doi:10.1074/jbc.M604323200
↑ Wang Y, Tomar A, George SP, Khurana S. Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial cell migration. Am J Physiol Cell Physiol. 2007 May;292(5):C1775-86. Epub 2007 Jan 17. PMID:17229814 doi:10.1152/ajpcell.00420.2006
↑ George SP, Wang Y, Mathew S, Srinivasan K, Khurana S. Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders. J Biol Chem. 2007 Sep 7;282(36):26528-41. Epub 2007 Jul 2. PMID:17606613 doi:10.1074/jbc.M703617200
↑ Revenu C, Courtois M, Michelot A, Sykes C, Louvard D, Robine S. Villin severing activity enhances actin-based motility in vivo. Mol Biol Cell. 2007 Mar;18(3):827-38. Epub 2006 Dec 20. PMID:17182858 doi:10.1091/mbc.E06-05-0423
↑ Khurana S, Tomar A, George SP, Wang Y, Siddiqui MR, Guo H, Tigyi G, Mathew S. Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia. Exp Cell Res. 2008 Feb 1;314(3):530-42. Epub 2007 Nov 12. PMID:18054784 doi:10.1016/j.yexcr.2007.10.028
↑ Wang Y, Srinivasan K, Siddiqui MR, George SP, Tomar A, Khurana S. A novel role for villin in intestinal epithelial cell survival and homeostasis. J Biol Chem. 2008 Apr 4;283(14):9454-64. doi: 10.1074/jbc.M707962200. Epub 2008, Jan 15. PMID:18198174 doi:10.1074/jbc.M707962200
↑ Tomar A, George SP, Mathew S, Khurana S. Differential effects of lysophosphatidic acid and phosphatidylinositol 4,5-bisphosphate on actin dynamics by direct association with the actin-binding protein villin. J Biol Chem. 2009 Dec 18;284(51):35278-82. doi: 10.1074/jbc.C109.060830. Epub . PMID:19808673 doi:10.1074/jbc.C109.060830
↑ Vermeulen W, Vanhaesebrouck P, Van Troys M, Verschueren M, Fant F, Goethals M, Ampe C, Martins JC, Borremans FA. Solution structures of the C-terminal headpiece subdomains of human villin and advillin, evaluation of headpiece F-actin-binding requirements. Protein Sci. 2004 May;13(5):1276-87. PMID:15096633 doi:10.1110/ps.03518104

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1unc"

@@ Line 1: / Line 1: @@
 ==Solution structure of the human villin C-terminal headpiece subdomain==
-<StructureSection load='1unc' size='340' side='right'caption='[[1unc]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
+<StructureSection load='1unc' size='340' side='right'caption='[[1unc]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1unc]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UNC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1unc]] 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=1UNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UNC FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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=1unc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1unc OCA], [https://pdbe.org/1unc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1unc RCSB], [https://www.ebi.ac.uk/pdbsum/1unc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1unc ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/VILI_HUMAN VILI_HUMAN] Note=Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure.
+== Function ==
+[https://www.uniprot.org/uniprot/VILI_HUMAN VILI_HUMAN] Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination.<ref>PMID:3087992</ref> <ref>PMID:11500485</ref> <ref>PMID:14594952</ref> <ref>PMID:15084600</ref> <ref>PMID:15272027</ref> <ref>PMID:15342783</ref> <ref>PMID:16921170</ref> <ref>PMID:17229814</ref> <ref>PMID:17606613</ref> <ref>PMID:17182858</ref> <ref>PMID:18054784</ref> <ref>PMID:18198174</ref> <ref>PMID:19808673</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 38: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ampe, C]]
+[[Category: Ampe C]]
-[[Category: Borremans, F]]
+[[Category: Borremans F]]
-[[Category: Fant, F]]
+[[Category: Fant F]]
-[[Category: Martins, J]]
+[[Category: Martins J]]
-[[Category: Troys, M Van]]
+[[Category: Van Troys M]]
-[[Category: Vanhaesebrouck, P]]
+[[Category: Vanhaesebrouck P]]
-[[Category: Vermeulen, W]]
+[[Category: Vermeulen W]]
-[[Category: Verschueren, M]]
+[[Category: Verschueren M]]
-[[Category: Actin binding]]
-[[Category: Cytoskeleton]]
-[[Category: F-actin binding]]
-[[Category: Headpiece subdomain]]

1unc

From Proteopedia

Current revision

Solution structure of the human villin C-terminal headpiece subdomain

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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