Cholesterol-sensing role of phenylalanine in the interaction of human islet amyloid polypeptide with lipid bilayers.
Cholesterol-sensing role of phenylalanine in the interaction of human islet amyloid polypeptide with lipid bilayers.
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苯丙氨酸在人胰岛淀粉样多肽与脂质双层相互作用中的胆固醇传感作用
DOI：
10.1039/c8ra07310d
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发表时间：
2018-12-04
期刊：
影响因子：
3.9
通讯作者：
Li, Fei
中科院分区：
文献类型：
--
作者：
Hao, Ruijie;Li, Yang;Guan, Liping;Lu, Tong;Meng, Feihong;Wang, Chunyu;Li, Fei
hIAPP与胰腺β细胞之间的相互作用与II型糖尿病中的β细胞死亡相关。胆固醇调节hIAPP-膜相互作用和hIAPP聚集。这背后的分子机制还没有很好地理解。在这里，我们探讨了F15在hIAPP和hIAPP 1 -19与脂质的各种组合物，包括DOPC，DPPC和DOPC/DPPC的相互作用中的胆固醇敏感作用，使用NMR，CD，ThT荧光和染料渗漏测定。我们表明，hIAPP和hIAPP 1 -19都是更有效的破坏与胆固醇的膜比他们在破坏膜没有胆固醇。在不存在胆固醇的情况下，亮氨酸取代F15会轻微影响肽与膜的结合和破坏，但在胆固醇存在下会大大降低活性。F15也在加速hIAPP的纤维状组装中起作用，但该功能本质上不依赖于胆固醇。胆固醇对hIAPP破坏性效力的促进作用在具有筏状结构域的膜中比在具有分散分布的胆固醇的膜中更有效。我们的研究结果表明，F15起着关键作用，在胆固醇传感结合和破坏的hIAPP PC膜和胆固醇在膜中的分布有影响的hIAPP的破坏活性。hIAPP与膜中胆固醇的相互作用由Phe 15介导。
The interactions between hIAPP and the pancreatic β-cells are associated with β-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 hIAPP1–19 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 hIAPP1–19 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. The interaction of hIAPP with cholesterol in the membrane is mediated by Phe15.
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影响因子：
3.4
作者：
Khemtemourian, Lucie;Engel, Maarten F. M.;Killian, J. Antoinette
通讯作者：
Killian, J. Antoinette
DOI：
10.1021/jp908092e
发表时间：
2010-04-08
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Pfefferkorn CM;Lee JC
通讯作者：
Lee JC
影响因子：
15
作者：
Brender, Jeffrey R.;Lee, Edgar L.;Ramamoorthy, Ayyalusamy
通讯作者：
Ramamoorthy, Ayyalusamy
影响因子：
6.2
作者：
Fantini J;Yahi N
通讯作者：
Yahi N
影响因子：
15
作者：
Smith PE;Brender JR;Ramamoorthy A
通讯作者：
Ramamoorthy A