Docking of Fatty Acids into the WIF Domain of the Human Wnt Inhibitory Factor-1

  title={Docking of Fatty Acids into the WIF Domain of the Human Wnt Inhibitory Factor-1},
  author={Tomas Malinauskas},
Palmitoylated Wnt proteins comprise a conserved family of secreted signaling molecules associated with variety of human cancers. WIF domain of the human WIF (Wnt inhibitory factor)-1 is sufficient for Wnt binding and signaling inhibition. Detailed interactions between Wnt and WIF-1 are not known. Computational docking was employed to identify a possible fatty acid binding site in the WIF domain. A putative binding site was identified inside the domain. WIF domain exhibited the highest affinity… 

Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1

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Prediction of Structure of Human WNT-CRD (FZD) Complex for Computational Drug Repurposing

The dimeric cysteine-rich domain was found to fit into the evolutionarily conserved U-shaped groove of WNT protein, thus providing a strong hydrophobic moiety for the frizzled receptor and serving as the largest binding pocket for WNT-FZD interaction.

The Role of Glypicans in Wnt Inhibitory Factor-1 Activity and the Structural Basis of Wif1's Effects on Wnt and Hedgehog Signaling

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ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes

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Wnt proteins.

The process of maturation of Wnt from its initial translation to its eventual release from a cell and interactions in the extracellular environment is described.

Secretion and extracellular space travel of Wnt proteins.

Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis

Wif-1 is identified as a novel extracellular Wnt modulator in cartilage biology and impaired growth of mesenchymal precursor cells and neutralised Wnt3a-mediated inhibition of chondrogenesis in micromass cultures of embryonic chick limb-bud cells.

Extracellular modulators of Wnt signalling.



NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.

Secreted antagonists of the Wnt signalling pathway

The extracellular antagonists of the Wnt signalling pathway can be divided into two broad classes: members of the sFRP (secreted Frizzled-related protein) family, WIF (Wnt inhibitory factor)-1 and Cerberus, primarily bind to Wnt proteins; the second class comprises certainMembers of the Dickkopf (Dkk) family; these families have as-yet-undiscovered functions.

Secreted Frizzled-related proteins: searching for relationships and patterns.

  • Steve JonesC. Jomary
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2002
The abundant expression of SFRP genes in the early embryo, altered expression patterns in disease states, and potential significance in the evolution of the vertebrate body plan, make these intriguing molecules relevant to investigations in diverse fields of biology and biomedical sciences.

Wnt proteins are lipid-modified and can act as stem cell growth factors

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A new secreted protein that binds to Wnt proteins and inhibits their activites

Wnt-inhibitory factor-1 (WIF-1) is described, a secreted protein that binds to Wnt proteins and inhibits their activities, and results indicate that WNT proteins interact with structurally diverse extracellular inhibitors to fine-tune the spatial and temporal patterns of Wnt activity.

A soluble form of Wnt-1 protein with mitogenic activity on mammary epithelial cells.

These results provide the first demonstration that a mammalian Wnt protein can act as a diffusible extracellular signaling factor.

Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth.

The results suggest the potential for further application of WIF-1 gene therapy in melanoma with Wif-1 silencing by in vitro and in vivo studies and confirm the effect of W IF-1 expression in suppressing tumor growth by inhibition of Wnt signaling in vivo.

The Wnt signaling pathway in development and disease.

The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs.

WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors

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Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction

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