Graduate School of Pharmaceutical Sciences , Tohoku University , Aoba-ku, Sendai 980-8578 , Japan.
J Phys Chem B. 2018 Jun 21;122(24):6364-6370. doi: 10.1021/acs.jpcb.8b03179. Epub 2018 Jun 8.
Peptide-lipid interactions are widely involved with biologically significant phenomena, including the pathogenic mechanisms of protein misfolding diseases and transmembrane protein folding. In this paper, the interaction of the cysteine/tryptophan (Cys/Trp) motif, which is a metal-binding motif of copper transporter (Ctr) proteins, with a lipid bilayer was studied using fluorescence and circular dichroism (CD) spectroscopy. The binding of Cu(I) to the Cys/Trp motif induced a large red-edge excitation shift in the Trp fluorescence, indicating that the Trp residue is located inside the lipid bilayer following complexation of Cu(I) with the Cys/Trp motif. The Stern-Volmer quenching of the Trp fluorescence also supported the Cu(I) binding peptide embedding in the lipid bilayer. The measurement of the CD spectra indicated the increase in β-sheet content of the Cys/Trp motif peptide as a result of Cu(I) binding. These results lead to the conclusion that complexation with Cu(I) induces the change in the secondary structure of the Cys/Trp motif, which results in the peptide embedding in the lipid bilayer. Cu(I)-induced enhancement of the lipid affinity is discussed in terms of the mechanism for copper transport by Ctr.
肽-脂相互作用广泛涉及具有生物学意义的现象，包括蛋白质错误折叠疾病和跨膜蛋白折叠的发病机制。在本文中，使用荧光和圆二色性（CD）光谱研究了半胱氨酸/色氨酸（Cys/Trp）基序与脂质双层的相互作用，该基序是铜转运蛋白（Ctr）蛋白的金属结合基序。Cu（I）与 Cys/Trp 基序的结合诱导色氨酸荧光的大边缘激发位移，表明 Trp 残基在 Cu（I）与 Cys/Trp 基序络合后位于脂质双层内部。色氨酸荧光的 Stern-Volmer 猝灭也支持 Cu（I）结合肽嵌入脂质双层。CD 光谱的测量表明，Cu（I）结合导致 Cys/Trp 基序肽的β-折叠含量增加。这些结果得出结论，Cu（I）与 Cys/Trp 基序的络合诱导该基序的二级结构发生变化，导致肽嵌入脂质双层。根据 Ctr 转运铜的机制讨论了 Cu（I）诱导的脂质亲和力增强。
