Embedding a Metal-Binding Motif for Copper Transporter into a Lipid Bilayer by Cu(I) Binding
Embedding a Metal-Binding Motif for Copper Transporter into a Lipid Bilayer by Cu(I) Binding
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通过 Cu(I) 结合将铜转运蛋白的金属结合基序嵌入脂质双层中
DOI：
10.1021/acs.jpcb.8b03179
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发表时间：
2018
影响因子：
3.3
通讯作者：
Tkakazu Nakabayashi
中科院分区：
文献类型：
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作者：
Mariko Okada;Shinji Kajimoto;Tkakazu Nakabayashi
肽-脂相互作用广泛涉及到许多重要的生物学现象，包括蛋白质错误折叠疾病和跨膜蛋白质折叠的致病机制。利用荧光光谱和圆二色光谱研究了铜转运蛋白（Ctr）的金属结合基序半胱氨酸/色氨酸（Cys/Trp）基序与脂质双层的相互作用。Cu（I）与Cys/Trp基序的结合诱导Trp荧光的大的红边激发位移，表明Trp残基在Cu（I）与Cys/Trp基序络合后位于脂质双层内。Trp荧光的Stern-Volmer猝灭也支持Cu（I）结合肽嵌入脂质双层中。CD光谱的测量表明，由于Cu（I）结合，Cys/Trp基序肽的β折叠含量增加。这些结果导致与Cu（I）的络合诱导Cys/Trp基序的二级结构的变化，这导致肽嵌入脂质双层中的结论。Cu（I）诱导的脂质亲和力的增强进行了讨论的铜转运的Ctr的机制。
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.