title: Structure of the C-terminal region of the Frizzled receptor 1 in detergent micelles.
abstract: 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/β-catenin signaling. We carried out structural studies for a peptide derived from the C-terminal domain of the FZD1 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.
authors.affiliation: Experimental Therapeutics Center, the Agency for Science, Technology and Research, Singapore 138669, Singapore.
authors.forename: Shovanlal
authors.initials: S
authors.lastname: Gayen
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Li
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: CongBao
authors.initials: C
authors.lastname: Kang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D003902:Detergents / Q000737:chemistry; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry; D010750:Phosphoproteins; D011487:Protein Conformation; D016415:Sequence Alignment; D051153:Wnt Proteins / Q000737:chemistry; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003902:Detergents; D000072261:Dishevelled Proteins; C489740:FZD1 protein, human; D051157:Frizzled Receptors; D008823:Micelles; D010446:Peptide Fragments; D010750:Phosphoproteins; D051153:Wnt Proteins; D051176:beta Catenin