Journal
MOLECULES
Volume 18, Issue 7, Pages 8579-8590Publisher
MDPI
DOI: 10.3390/molecules18078579
Keywords
helix 8; Frizzled receptor; detergent micelles; NMR
Funding
- A*STAR Investigatorship
- A*STAR JCO grant [10/03/FG/06/06]
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The C-terminal domains of the Frizzleds (FZDs) contain a short conserved motif (KTXXXW). It has been demonstrated that FZDs interacted with the PDZ domain of the cytoplasmic proteins such as Dishevelled through this motif and mutations in this motif disrupted Wnt/beta-catenin signaling. We carried out structural studies for a peptide derived from the C-terminal domain of the FZD(1) in different solvents using circular dichroism and solution NMR spectroscopy. Our results showed that this domain was unstructured in an aqueous solution and formed a helical structure in detergent micelles. Fluorescence studies suggested that the tryptophan residue (W630) in the motif interacted with micelles. The solution structure of the peptide in sodium dodecyl sulfate micelles was determined and an amphipathic helix was identified. This helix may have similar function to the helix 8 of other G protein-coupled receptors.
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