Thermodynamics of amyloid fibril formation from chemical depolymerization.
Thermodynamics of amyloid fibril formation from chemical depolymerization.
复制标题
化学解聚形成淀粉样原纤维的热力学。
DOI：
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Alexander K. Buell
中科院分区：
文献类型：
--
作者：
N. Vettore;Alexander K. Buell
淀粉样原纤维是一种同分子蛋白聚合物，在疾病和生物功能中起重要作用。虽然人们对它们的动力学和形成机制了解很多，但它们的热力学稳定性的起源和大小却很少受到关注。尽管淀粉样蛋白原纤维的热力学稳定性是其寿命和体内加工的重要决定因素。在这里，我们使用化学变性剂在不同浓度下解聚两种不同蛋白质（PI3K-SH3和胰高血糖素）的淀粉样蛋白原纤维，并表明以前应用的等密度线性聚合模型是一种过度简化，不能捕获淀粉样蛋白原纤维化学解聚的浓度依赖性。我们表明，协同聚合，这是兼容的图片淀粉样蛋白形成的成核聚合过程，能够定量地描述热力学数据。我们使用这种结合实验和概念框架，以探索淀粉样蛋白纤维稳定性的离子强度依赖性。结合先前发表的关于淀粉样纤维生长动力学的离子强度依赖性的数据，我们的研究结果为淀粉样纤维生长过渡状态的产品性质提供了强有力的证据。
Amyloid fibrils are homo-molecular protein polymers that play an important role in disease and biological function. While much is known about their kinetics and mechanisms of formation, the origin and magnitude of their thermodynamic stability has received significantly less attention. This is despite the fact that the thermodynamic stability of amyloid fibrils is an important determinant of their lifetimes and processing in vivo. Here we use depolymerization by chemical denaturants of amyloid fibrils of two different proteins (PI3K-SH3 and glucagon) at different concentrations and show that the previously applied isodesmic linear polymerization model is an oversimplification that does not capture the concentration dependence of chemical depolymerization of amyloid fibrils. We show that cooperative polymerization, which is compatible with the picture of amyloid formation as a nucleated polymerization process, is able to quantitatively describe the thermodynamic data. We use this combined experimental and conceptual framework in order to probe the ionic strength dependence of amyloid fibril stability. In combination with previously published data on the ionic strength dependence of amyloid fibril growth kinetics, our results provide strong evidence for the product-like nature of the transition state of amyloid fibril growth.
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影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
3.4
作者：
Kollipara, Laxmikanth;Zahedi, Rene P.
通讯作者：
Zahedi, Rene P.
DOI：
10.1021/jp9050098
发表时间：
2009-10-29
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
O'Brien EP;Okamoto Y;Straub JE;Brooks BR;Thirumalai D
通讯作者：
Thirumalai D
影响因子：
15
作者：
Baldwin, Andrew J.;Knowles, Tuomas P. J.;Dobson, Christopher M.
通讯作者：
Dobson, Christopher M.