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]
Publication Abstract from PubMed
Many small proteins fold highly cooperatively in an all-or-none fashion and thus their native states are well protected from thermal fluctuations by an extensive network of interactions across the folded structure. Because protein structures are stabilized by local and nonlocal interactions among distal residues, dissecting individual substructures from the context of folded proteins results in large destabilization and loss of unique three-dimensional structure. Thus, mini-protein substructures can only rarely be derived from natural templates. Here, we describe a compact native 24-residues-long supersecondary structure derived from the hyperstable villin headpiece subdomain consisting of helices 2 and 3 (HP24). Using a combination of experimental techniques, including NMR and small-angle x-ray scattering, as well as all-atom replica exchange molecular-dynamics simulations, we show that a variant with stabilizing substitutions (HP24stab) forms a densely packed and compact conformation. In HP24stab, interactions between helices 2 and 3 are similar to those observed in native folded HP35, and the two helices cooperatively stabilize each other by completing the hydrophobic core lining the central part of HP35. Interestingly, even though the HP24wt fragment shows a more expanded and less structured conformation, NMR and simulations demonstrate a preference for a native-like topology. Thus, the two stabilizing residues in HP24stab shift the energy balance toward the native state, leading to a minimal folding motif.
A compact native 24-residue supersecondary structure derived from the villin headpiece subdomain.,Hocking HG, Hase F, Madl T, Zacharias M, Rief M, Zoldak G Biophys J. 2015 Feb 3;108(3):678-86. doi: 10.1016/j.bpj.2014.11.3482. PMID:25650934[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
- ↑ Hocking HG, Hase F, Madl T, Zacharias M, Rief M, Zoldak G. A compact native 24-residue supersecondary structure derived from the villin headpiece subdomain. Biophys J. 2015 Feb 3;108(3):678-86. doi: 10.1016/j.bpj.2014.11.3482. PMID:25650934 doi:http://dx.doi.org/10.1016/j.bpj.2014.11.3482
