View source for 9mfa


==Backbone alpha-Methylation in the Villin Headpiece Miniprotein: HP35 with Aib at Position 30==
<StructureSection load='9mfa' size='340' side='right'caption='[[9mfa]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9mfa]] 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=9MFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MFA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</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=9mfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mfa OCA], [https://pdbe.org/9mfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mfa RCSB], [https://www.ebi.ac.uk/pdbsum/9mfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mfa ProSAT]</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> 
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== Publication Abstract from PubMed ==
The alpha-helix is an abundant and functionally important element of protein secondary structure, which has motivated intensive efforts toward chemical strategies to stabilize helical folds. One such method is the incorporation of non-canonical backbone composition through an additional methyl substituent at the Calpha atom. Examples of monomers include the achiral 2-aminoisobutyric acid (Aib) with geminal dimethyl substitution and chiral analogues with one methyl and one non-methyl substituent. While Aib and chiral Calpha-Me residues are both established helix promoting moieties, their comparative ability in this regard has not been quantitatively investigated. Addressing this gap would help to inform the use of these building blocks in the construction of peptide and protein mimetics as well as provide fundamental insights into consequences of backbone methylation on folding. Here, we report a quantitative comparison of the impacts of Aib and chiral alphaMe residues on the high-resolution folded structure and folding thermodynamics of a small helical protein. These results reveal a synergistic stabilizing effect arising from the presence of Calpha methylation in conjunction with a Calpha stereocenter.

Interplay between Calpha Methylation and Calpha Stereochemistry in the Folding Energetics of a Helix-Rich Miniprotein.,Harmon TW, Lin Y, Sutton RT, Osborne SWJ, Horne WS Chembiochem. 2025 Jan 10:e202401022. doi: 10.1002/cbic.202401022. PMID:39791987<ref>PMID:39791987</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9mfa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Harmon TW]]
[[Category: Horne WS]]
[[Category: Lin Y]]
[[Category: Osborne S]]
[[Category: Sutton RT]]