Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles
Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles
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DOI：
10.3390/molecules18078579
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发表时间：
2013-07-01
期刊：
影响因子：
4.6
通讯作者：
Kang, CongBao
中科院分区：
文献类型：
--
作者：
Gayen, Shovanlal;Li, Qingxin;Kang, CongBao
Frizzleds (FZD) 的 C 端结构域包含一个短保守基序 (KTXXXW)。已经证明，FZD 通过该基序与细胞质蛋白（例如 Disheveled）的 PDZ 结构域相互作用，并且该基序中的突变破坏了 Wnt/β-连环蛋白信号传导。我们使用圆二色性和溶液核磁共振光谱法，在不同溶剂中对衍生自 FZD(1) C 端结构域的肽进行了结构研究。我们的结果表明，该结构域在水溶液中是非结构化的，并在洗涤剂胶束中形成螺旋结构。荧光研究表明基序中的色氨酸残基 (W630) 与胶束相互作用。确定了十二烷基硫酸钠胶束中肽的溶液结构，并鉴定了两亲性螺旋。该螺旋可能与其他 G 蛋白偶联受体的螺旋 8 具有相似的功能。
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.