Probing the pressure-temperature stability of amyloid fibrils provides new insights into their molecular properties
Probing the pressure-temperature stability of amyloid fibrils provides new insights into their molecular properties
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DOI：
10.1016/j.bbapap.2005.10.021
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Dobson, CM
中科院分区：
文献类型：
--
作者：
Meersman, F;Dobson, CM
包括阿尔茨海默病和II型糖尿病在内的许多医学病症的特征在于淀粉样蛋白原纤维在组织中的沉积。原纤维的不溶性和尺寸在很大程度上排除了在高分辨率下测定其结构。探索淀粉样蛋白原纤维稳定性的研究可以揭示哪些非共价相互作用在原纤维结构的形成和维持中是重要的。特别是，我们在这里审查使用高静水压力和高温扰动技术。一般来说，在组装过程早期形成的小聚集体可以通过高压解离，但成熟的淀粉样蛋白原纤维是高度压力稳定的。这一发现表明，在此期间发生的侧链包装和氢键形成的优化，而疏水效应和静电相互作用在早期阶段的聚集起主导作用的时间过渡。然而，高温可以破坏大多数聚集体。虽然观察到的淀粉样蛋白原纤维的稳定性并不是这些结构所独有的，但淀粉样蛋白原纤维可以代表自由能的全局最小值的概念得到了这种类型的研究的支持。一些关于有毒物种的性质，与至少许多淀粉样蛋白疾病，最近提出的结构模型的影响进行了讨论。(c)2005 Elsevier B.V.保留所有权利。
A number of medical disorders, including Alzheimer's disease and type II diabetes, is characterised by the deposition of amyloid fibrils in tissue. The insolubility and size of the fibrils has largely precluded the determination of their structures at high resolution. Studies probing the stability of amyloid fibrils can reveal which non-covalent interactions are important in the formation and maintenance of the fibril structure. In particular, we review here the use of high hydrostatic pressure and high temperature as perturbation techniques. In general, small aggregates formed early in the assembly process can be dissociated by high pressure, but mature amyloid fibrils are highly pressure stable. This finding suggests that a temporal transition occurs during which side chain packing and hydrogen bond formation are optimised, whereas the hydrophobic effect and electrostatic interactions play a dominant role in the early stages of the aggregation. High temperatures, however, can disrupt most aggregates. Though the observed stability of amyloid fibrils is not unique to these structures, the notion that amyloid fibrils can represent the global minimum in free energy is supported by this type of investigations. Some implications regarding the nature of toxic species, associated with at least many of the amyloid disorders, and recently proposed structural models are discussed. (c) 2005 Elsevier B.V. All rights reserved.