|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==NMR solution Structure of the Villin Headpiece Mutant G34L== | | ==NMR solution Structure of the Villin Headpiece Mutant G34L== |
| - | <StructureSection load='2ppz' size='340' side='right' caption='[[2ppz]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2ppz' size='340' side='right'caption='[[2ppz]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ppz]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PPZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ppz]] 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=2PPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PPZ FirstGlance]. <br> |
| - | </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=2ppz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ppz OCA], [http://pdbe.org/2ppz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ppz RCSB], [http://www.ebi.ac.uk/pdbsum/2ppz PDBsum]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ppz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ppz OCA], [https://pdbe.org/2ppz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ppz RCSB], [https://www.ebi.ac.uk/pdbsum/2ppz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ppz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pp/2ppz_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pp/2ppz_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| Line 33: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gronwald, W]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Hoffmann, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Hohm, T]] | + | [[Category: Gronwald W]] |
| - | [[Category: Alpha helical]] | + | [[Category: Hoffmann D]] |
| - | [[Category: In silico sequence optimization]] | + | [[Category: Hohm T]] |
| - | [[Category: Small stable core]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Thermostable]]
| + | |
| 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
BACKGROUND: As a rule, peptides are more flexible and unstructured than proteins with their substantial stabilizing hydrophobic cores. Nevertheless, a few stably folding peptides have been discovered. This raises the question whether there may be more such peptides that are unknown as yet. These molecules could be helpful in basic research and medicine. RESULTS: As a method to explore the space of conformationally stable peptides, we have developed an evolutionary algorithm that allows optimization of sequences with respect to several criteria simultaneously, for instance stability, accessibility of arbitrary parts of the peptide, etc. In a proof-of-concept experiment we have perturbed the sequence of the peptide Villin Headpiece, known to be stable in vitro. Starting from the perturbed sequence we applied our algorithm to optimize peptide stability and accessibility of a loop. Unexpectedly, two clusters of sequences were generated in this way that, according to our criteria, should form structures with higher stability than the wild-type. The structures in one of the clusters possess a fold that markedly differs from the native fold of Villin Headpiece. One of the mutants predicted to be stable was selected for synthesis, its molecular 3D-structure was characterized by nuclear magnetic resonance spectroscopy, and its stability was measured by circular dichroism. Predicted structure and stability were in good agreement with experiment. Eight other sequences and structures, including five with a non-native fold are provided as bona fide predictions. CONCLUSION: The results suggest that much more conformationally stable peptides may exist than are known so far, and that small fold classes could comprise well-separated sub-folds.
Evolutionary Pareto-optimization of stably folding peptides.,Gronwald W, Hohm T, Hoffmann D BMC Bioinformatics. 2008 Feb 19;9:109. PMID:18284690[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
- ↑ Gronwald W, Hohm T, Hoffmann D. Evolutionary Pareto-optimization of stably folding peptides. BMC Bioinformatics. 2008 Feb 19;9:109. PMID:18284690 doi:10.1186/1471-2105-9-109
|
