二价铜离子对人胰岛淀粉样蛋白(hIAPP)(1128)多肽聚集的影响

doi:10.11944/j.issn.1000-0518.2018.02.170378

摘要/Abstract

摘要：

人胰岛淀粉样蛋白(hIAPP)与Ⅱ型糖尿病(T2DM)密切相关,被认为是导致胰岛β细胞凋亡的致病因素之一,研究发现环境因素(如金属离子、pH值和温度等)对hIAPP的聚集过程有很大影响。本文采用多种生物物理的实验方法,研究了二价铜离子对hIAPP及其片段聚集的影响。原子力显微镜(AFM)和硫代黄素T(ThT)荧光的测量表明,铜离子能够明显地抑制hIAPP(1128)聚集成纤维,其抑制程度随铜离子浓度的增加而明显加剧。显微傅里叶变换红外光谱(Micro-FTIR)的结果表明,铜离子能够抑制hIAPP多肽中α螺旋结构向β折叠的转变。另外,氨基酸定点突变实验结果表明,hIAPP(1128)中的组氨酸(His18)可能对多肽的聚集行为和金属铜离子的相互作用起到了决定性的影响。

关键词: 铜离子, 人胰岛淀粉样蛋白, Ⅱ型糖尿病

Abstract:

Human islet amyloid polypeptide(hIAPP) is closely associated with type 2 diabetes mellitus(T2DM), which is one of possible pathogenic factors of islet beta cell apoptosis. It has been suggested that the environmental factors(such as metal ions, pH and temperature) have great effects on the aggregation process of hIAPP. In this study, we investigate the influence of copper(Ⅱ) ions on the aggregation of hIAPP and its fragments by a variety of biophysical methods. Atomic force microscope(AFM) and thioflavin T(ThT) fluorescence measurements show that the copper ions can inhibit hIAPP(137) and hIAPP(1128) to aggregate into fibers. In addition, the micro-Fourier transform infrared spectroscopy(Micro-FTIR) shows that copper ions can restrain the transition from alpha helices structure to beta sheets formation during the peptide incubation. By the single amino acid mutation experiment, we speculate that the His18 in hIAPP(1128) may have a dominant effect on the aggregation behavior and the interaction with copper ions.

Key words: copper(Ⅱ) ions, human islet amyloid protein, type 2 diabetes

陆澄, 李琳, 鄢鹏, 张楠, 陈武超, 张公军, 周星飞. 二价铜离子对人胰岛淀粉样蛋白(hIAPP)(1128)多肽聚集的影响[J]. 应用化学, 2018, 35(2): 147-153.

LU Cheng, LI Lin, YAN Peng, ZHANG Nan, CHEN Wuchao, ZHANG Gongjun, ZHOU Xingfei. Effect of Copper Ions on the Aggregation of Human Islet Amyloid Polypeptide(1128)[J]. Chinese Journal of Applied Chemistry, 2018, 35(2): 147-153.

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