5i1s

Villin headpiece subdomain with a Lys30 to APC substitution

spinqualitylabelsall models 5i1s, resolution 1.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i1s is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: DAL, DAR, DAS, DGL, DGN, DHI, DLE, DLY, DPN, DPR, DSG, DSN, DTH, DTR, DVA, MED, XPC Related: 3trw, 3trv, 3tjw, 3try, 5i1o, 5i1n Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Synthetic peptides that contain backbone modifications but nevertheless adopt folded structures similar to those of natural polypeptides are of fundamental interest and may provide a basis for biomedical applications. Such molecules can, for example, mimic the ability of natural prototypes to bind to specific target macromolecules but resist degradation by proteases. We have previously shown that oligomers containing mixtures of alpha- and beta-amino acid residues ("alpha/beta-peptides") can mimic the alpha-helix secondary structure, and that properly designed alpha/beta-peptides can bind to proteins that evolved to bind to alpha-helical partners. Here we report fundamental studies that support the long-range goal of extending the alpha/beta approach to tertiary structures. We have evaluated the impact of single alpha --> beta modifications on the structure and stability of the small and well-studied villin headpiece subdomain (VHP). The native state of this 35-residue polypeptide contains several alpha-helical segments packed around a small hydrophobic core. We examined alpha --> beta substitution at four solvent-exposed positions, Asn19, Trp23, Gln26 and Lys30. In each case, both the beta(3) homologue of the natural alpha residue and a cyclic beta residue were evaluated. All alpha --> beta(3) substitutions caused significant destabilization of the tertiary structure as measured by variable-temperature circular dichroism, although at some of these positions, replacing the beta(3) residue with a cyclic beta residue led to improved stability. Atomic-resolution structures of four VHP analogues were obtained via quasiracemic crystallization. These findings contribute to a fundamental alpha/beta-peptide knowledge-base by confirming that beta(3)-amino acid residues can serve as effective structural mimics of homologous alpha-amino acid residues within a natural tertiary fold, which should support rational design of functional alpha/beta analogues of natural poly-alpha-peptides. Effects of Single alpha-to-beta Residue Replacements on Structure and Stability in a Small Protein: Insights from Quasiracemic Crystallization.,Kreitler DF, Mortenson DE, Forest KT, Gellman SH J Am Chem Soc. 2016 May 25;138(20):6498-505. doi: 10.1021/jacs.6b01454. Epub 2016, May 12. PMID:27171550 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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