Main-chain dominated amyloid structures demonstrated by the effect of high pressure
Main-chain dominated amyloid structures demonstrated by the effect of high pressure
复制标题
DOI：
10.1016/j.jmb.2005.07.043
复制
发表时间：
2005-09-30
影响因子：
5.6
通讯作者：
Goto, Y
中科院分区：
文献类型：
--
作者：
Chatani, E;Kato, M;Goto, Y
有人提出，虽然蛋白质的球状天然形式是通过追求具有氨基酸残基的最佳包装的独特折叠而进化的侧链主导的紧凑结构，但淀粉样蛋白原纤维是具有广泛氢键网络的主链主导的结构。为了解决这个问题，研究了静水压力对透析相关淀粉样变性中β 2-微球蛋白（β 2-m）淀粉样纤维的影响。通过监测硫磺素T荧光，光散射和色氨酸荧光在各种压力和浓度的盐酸胍进行的系统分析显示连续发生的对比构象变化：首先，压力诱导的原纤维重组，然后压力诱导的展开。体积的变化以及观察到的结构变化表明，β 2-m淀粉样蛋白原纤维在环境压力下不太紧密地堆积有大量的空腔，与主链主导的淀粉样蛋白结构一致。此外，没有最佳包装的淀粉样蛋白结构将使各种异构体形成，这表明与独特的天然折叠相反，淀粉样蛋白原纤维的多种形式的结构基础。(c)2005爱思唯尔有限公司保留所有权利。
It has been suggested that, while the globular native forms of proteins are a side-chain-dominated compact structure evolved by pursuing a unique fold with optimal packing of amino acid residues, amyloid fibrils are a main-chain-dominated structure with an extensive hydrogen bond network. To address this issue, the effects of hydrostatic pressure on amyloid fibrils of beta(2)-Microglobulin (beta 2-m), involved in dialysis-related amyloidosis, were studied. A systematic analysis at various pressures and concentrations of guanidine hydrochloride conducted by monitoring thioflavin T fluorescence, light-scattering, and tryptophan fluorescence revealed contrasting conformational changes occurring consecutively: first, a pressure-induced reorganization of fibrils and then a pressure-induced unfolding. The changes in volume as well as the observed structural changes indicate that the beta 2-m amyloid fibrils under ambient pressure are less tightly packed with a larger number of cavities, consistent with the main-chain-dominated amyloid structure. Moreover, the amyloid structure without optimal packing will enable various isoforms to form, suggesting the structural basis of multiple forms of amyloid fibrils in contrast to the unique native-fold. (c) 2005 Elsevier Ltd. All rights reserved.