Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid.
Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid.
复制标题
DOI：
10.1021/jp810261x
复制
发表时间：
2009-02-26
期刊：
影响因子：
--
通讯作者：
Zanni MT
中科院分区：
文献类型：
--
作者：
Ling YL;Strasfeld DB;Shim SH;Raleigh DP;Zanni MT
胰岛淀粉样多肽（IAPP，也称为胰淀素）是2型糖尿病胰腺淀粉样沉积的原因。沉积物以及其组装中的中间体对胰腺β细胞具有细胞毒性，并导致与2型糖尿病相关的β细胞质量损失。体内触发胰岛淀粉样蛋白沉积的因素尚不清楚，但肽膜相互作用已被假定在胰岛淀粉样蛋白形成中起重要作用。为了更好地理解膜相互作用在淀粉样蛋白形成中的作用，使用二维红外光谱来比较在存在和不存在带负电荷的脂质囊泡的情况下人IAPP的淀粉样蛋白形成的动力学。从两组实验的光谱特征和动力学痕迹的比较提供了证据，在膜介导的装配IAPP淀粉样蛋白的有序中间体的形成。在淀粉样蛋白形成过程中检测到一个特征性的瞬态光谱特征，在囊泡的存在下，这是没有观察到的囊泡。与中间体相关的光谱特征在自组装过程中强度升高，随后以动力学中间体的经典方式强度衰减。对大鼠IAPP（一种已知与膜相互作用但不形成淀粉样蛋白的变体）的研究证实了中间体的存在。讨论了具体结构特征的二维红外光谱分析。二维红外光谱的时间和二级结构分辨率的独特组合使hIAPP中间体的时间演变首次被直接监测。这里提供的数据表明了二维红外光谱研究膜催化淀粉样蛋白形成的效用。
Islet amyloid polypeptide (IAPP, also known as amylin) is responsible for pancreatic amyloid deposits in type 2 diabetes. The deposits, as well as intermediates in their assembly, are cytotoxic to pancreatic β-cells and contribute to the loss of β-cell mass associated with type 2 diabetes. The factors which trigger islet amyloid deposition in vivo are not well understood but peptide membrane interactions have been postulated to play an important role in islet amyloid formation. To better understand the role of membrane interactions in amyloid formation two-dimensional infrared spectroscopy was used to compare the kinetics of amyloid formation for human IAPP both in the presence and in the absence of negatively charged lipid vesicles. Comparison of spectral features and kinetic traces from the two sets of experiments provides evidence for the formation of an ordered intermediate during the membrane-mediated assembly of IAPP amyloid. A characteristic transient spectral feature is detected during amyloid formation in the presence of vesicles which is not observed in the absence of vesicles. The spectral feature associated with the intermediate raises in intensity during the self assembly process and subsequently decays in intensity in the classic manner of a kinetic intermediate. Studies with rat IAPP, a variant which is known to interact with membranes but does not form amyloid, confirm the presence of an intermediate. The analysis of 2D IR spectra in terms of specific structural features is discussed. The unique combination of time and secondary structure resolution of 2D IR spectroscopy has enabled the time-evolution of a hIAPP intermediate to be directly monitored for the first time. The data presented here demonstrates the utility of 2D IR spectroscopy for studying membrane-catalyzed amyloid formation.
登录
查看更多内容
影响因子：
2.9
作者：
Jayasinghe, SA;Langen, R
通讯作者：
Langen, R
影响因子：
2.9
作者：
Luca, Sorin;Yau, Wai-Ming;Tycko, Robert
通讯作者：
Tycko, Robert
影响因子：
4.4
作者：
Mukherjee, P;Krummel, AT;Zanni, MT
通讯作者：
Zanni, MT
DOI：
10.1016/0167-4838(92)90411-6
发表时间：
1992-08-21
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MCLEAN, LR;BALASUBRAMANIAM, A
通讯作者：
BALASUBRAMANIAM, A
影响因子：
15
作者：
GRIFFITHS, JM;ASHBURN, TT;LANSBURY, PT
通讯作者：
LANSBURY, PT