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首页> 外文期刊>RSC Advances >Cholesterol- sensing role of phenylalanine in the interaction of human islet amyloid polypeptide with lipid bilayers
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Cholesterol- sensing role of phenylalanine in the interaction of human islet amyloid polypeptide with lipid bilayers

机译：苯丙氨酸在人胰岛淀粉样蛋白多肽与脂质双层的相互作用中的胆固醇感测作用

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摘要

The interactions between hIAPP and the pancreatic -cells are associated with -cell death in type II diabetes. Cholesterol modulates hIAPP-membrane interaction and hIAPP aggregation. The molecular mechanism underlying this is not well understood. Here we explore the cholesterol-sensing role of F15 in the interactions of hIAPP and hIAPP(1-19) with various compositions of lipids, including DOPC, DPPC and DOPC/DPPC using NMR, CD, ThT fluorescence and dye leakage assays. We show that both hIAPP and hIAPP(1-19) are more potent in the disruption to the membranes with cholesterol than they are in the disruption to the membranes without cholesterol. A substitution of F15 by leucine affects the binding and disruption of the peptides to the membranes slightly in the absence of cholesterol, but decreases the activities largely in the presence of cholesterol. F15 also plays a role in accelerating fibrillar assembly of hIAPP, but the function is independent of cholesterol in nature. The promotion of cholesterol to the disruptive potency of hIAPP is more effective in the membrane with raft-like domains than in the membrane with a dispersed distribution of cholesterol. Our results suggest that F15 plays a key role in the cholesterol-sensing binding and disruption of hIAPP to the PC membranes and the distribution of cholesterol in the membranes has an influence on the disruptive activity of hIAPP.
机译：HIAPP和胰腺 - 细胞之间的相互作用与II型糖尿病中的细胞死亡有关。胆固醇调节HIAPP膜相互作用和HIAPP聚集。依据的分子机制并不顺利。在这里，我们探讨了F15在HIAPP和HIAPP（1-19）的相互作用中具有各种脂质组合物的胆固醇感测作用，包括使用NMR，CD，THT荧光和染料泄漏测定的DOPC，DPPC和DOPPC。我们表明HIAPP和HIAPP（1-19）在胆固醇中的破坏中更有效，而不是在没有胆固醇的情况下对膜中断。亮氨酸的替代物在没有胆固醇的情况下略微影响肽对膜的结合和破坏，但在很大程度上在胆固醇存在下降低了活性。 F15还在加速HIAPP的纤维状组装方面发挥作用，但该功能与胆固醇本质上无关。促进胆固醇对HIAPP的破坏性效力在膜中更有效，筏状结构域比膜中的膜中的膜中的分散分布在膜中。我们的研究结果表明，F15在胆固醇传感的结合和中断到PC膜的破坏以及膜中胆固醇的分布对HIAPP的破坏性活性作出关键作用。

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  • 来源
    《RSC Advances》 |2018年第71期|共8页
  • 作者

    Hao Ruijie; Li Yang; Guan Liping; Lu Tong; Meng Feihong; Wang Chunyu; Li Fei;

  • 作者单位

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

    Jilin Univ State Key Lab Supramol Struct &

    Mat 2699 Qianjin Ave Changchun Jilin 130012 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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