Abstract
The human Wnt-binding protein Wnt-inhibitory factor-1 (WIF-1) comprises an N-terminal WIF module followed by five EGF-like repeats. Here we report the three-dimensional structure of the WIF domain of WIF-1 determined by NMR spectroscopy. The fold consists of an eight-stranded beta-sandwich reminiscent of the immunoglobulin fold. Residual detergent (Brij-35) used in the refolding protocol was found to bind tightly to the WIF domain. The binding site was identified by intermolecular nuclear Overhauser effects observed between the WIF domain and the alkyl chain of the detergent. The results point to a possible role of WIF domains as a recognition motif of Wnt and Drosophila Hedgehog proteins that are activated by palmitoylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Crystallography, X-Ray
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Drosophila Proteins / metabolism
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Hedgehog Proteins
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Humans
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Magnetic Resonance Spectroscopy*
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Molecular Sequence Data
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Polidocanol
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Polyethylene Glycols / metabolism
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Protein Structure, Tertiary
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sequence Alignment
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Wnt Proteins / antagonists & inhibitors*
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Wnt Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Drosophila Proteins
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Hedgehog Proteins
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Repressor Proteins
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WIF1 protein, human
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Wnt Proteins
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Polidocanol
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hh protein, Drosophila
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Polyethylene Glycols