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| - | [[Image:2jm0.gif|left|200px]] | |
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| - | <!-- | + | ==Solution structure of chicken villin headpiece subdomain containing a fluorinated side chain in the core== |
| - | The line below this paragraph, containing "STRUCTURE_2jm0", creates the "Structure Box" on the page.
| + | <StructureSection load='2jm0' size='340' side='right'caption='[[2jm0]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2jm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JM0 FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PF5:2,3,4,5,6-PENTAFLUORO-L-PHENYLALANINE'>PF5</scene></td></tr> |
| - | {{STRUCTURE_2jm0| PDB=2jm0 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jm0 OCA], [https://pdbe.org/2jm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2jm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jm0 ProSAT], [https://www.topsan.org/Proteins/CESG/2jm0 TOPSAN]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/VILI_CHICK VILI_CHICK] 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 (By similarity). Its actin-bundling activity is inhibited by tropomyosin.<ref>PMID:3793760</ref> <ref>PMID:1618806</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/2jm0_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jm0 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe --> F(5)-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F(5)-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 --> F(5)-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by approximately 1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe --> F(5)-Phe mutations offer the possibility of greater tertiary structural stability from side chain-side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability. |
| | | | |
| - | '''Solution structure of chicken villin headpiece subdomain containing a fluorinated side chain in the core'''
| + | Solution structure of a small protein containing a fluorinated side chain in the core.,Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:17123960<ref>PMID:17123960</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe --> F(5)-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F(5)-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 --> F(5)-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by approximately 1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe --> F(5)-Phe mutations offer the possibility of greater tertiary structural stability from side chain-side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2JM0 is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JM0 OCA].
| + | </div> |
| | + | <div class="pdbe-citations 2jm0" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Solution structure of a small protein containing a fluorinated side chain in the core., Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC, Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17123960 17123960]
| + | *[[Villin|Villin]] |
| - | [[Category: Single protein]] | + | == References == |
| - | [[Category: Cornilescu, C C.]]
| + | <references/> |
| - | [[Category: Cornilescu, G.]] | + | __TOC__ |
| - | [[Category: Gellman, S H.]] | + | </StructureSection> |
| - | [[Category: Hadley, E B.]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Markley, J L.]] | + | [[Category: Large Structures]] |
| - | [[Category: Chicken villin headpiece]] | + | [[Category: Cornilescu CC]] |
| - | [[Category: Fluorinated phe]] | + | [[Category: Cornilescu G]] |
| - | [[Category: Vhp]] | + | [[Category: Gellman SH]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:00:49 2008''
| + | [[Category: Hadley EB]] |
| | + | [[Category: Markley JL]] |
| Structural highlights
Function
VILI_CHICK 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 (By similarity). Its actin-bundling activity is inhibited by tropomyosin.[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
We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe --> F(5)-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F(5)-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 --> F(5)-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by approximately 1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe --> F(5)-Phe mutations offer the possibility of greater tertiary structural stability from side chain-side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability.
Solution structure of a small protein containing a fluorinated side chain in the core.,Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:17123960[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Burgess DR, Broschat KO, Hayden JM. Tropomyosin distinguishes between the two actin-binding sites of villin and affects actin-binding properties of other brush border proteins. J Cell Biol. 1987 Jan;104(1):29-40. PMID:3793760
- ↑ de Arruda MV, Bazari H, Wallek M, Matsudaira P. An actin footprint on villin. Single site substitutions in a cluster of basic residues inhibit the actin severing but not capping activity of villin. J Biol Chem. 1992 Jun 25;267(18):13079-85. PMID:1618806
- ↑ Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC. Solution structure of a small protein containing a fluorinated side chain in the core. Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:17123960 doi:10.1110/ps.062557707
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