3fg7

The crystal structure of villin domain 6The crystal structure of villin domain 6

Structural highlights 3fg7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease VILI_HUMAN Note=Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure. Function VILI_HUMAN 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. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. 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 Villin and gelsolin consist of six homologous domains of the gelsolin/cofilin fold (V1-V6 and G1-G6, respectively). Villin differs from gelsolin in possessing at its C terminus an unrelated seventh domain, the villin headpiece. Here, we present the crystal structure of villin domain V6 in an environment in which intact villin would be inactive, in the absence of bound Ca(2+) or phosphorylation. The structure of V6 more closely resembles that of the activated form of G6, which contains one bound Ca(2+), rather than that of the calcium ion-free form of G6 within intact inactive gelsolin. Strikingly apparent is that the long helix in V6 is straight, as found in the activated form of G6, as opposed to the kinked version in inactive gelsolin. Molecular dynamics calculations suggest that the preferable conformation for this helix in the isolated G6 domain is also straight in the absence of Ca(2+) and other gelsolin domains. However, the G6 helix bends in intact calcium ion-free gelsolin to allow interaction with G2 and G4. We suggest that a similar situation exists in villin. Within the intact protein, a bent V6 helix, when triggered by Ca(2+), straightens and helps push apart adjacent domains to expose actin-binding sites within the protein. The sixth domain in this superfamily of proteins serves as a keystone that locks together a compact ensemble of domains in an inactive state. Perturbing the keystone initiates reorganization of the structure to reveal previously buried actin-binding sites. Helix straightening as an activation mechanism in the gelsolin superfamily of actin regulatory proteins.,Wang H, Chumnarnsilpa S, Loonchanta A, Li Q, Kuan YM, Robine S, Larsson M, Mihalek I, Burtnick LD, Robinson RC J Biol Chem. 2009 Aug 7;284(32):21265-9. Epub 2009 Jun 1. PMID:19491107 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Villin

spinqualitylabelsall models 3fg7, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image