The effect of nanoparticles on amyloid aggregation depends on the protein stability and intrinsic aggregation rate.
The effect of nanoparticles on amyloid aggregation depends on the protein stability and intrinsic aggregation rate.
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DOI：
10.1021/la203078w
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发表时间：
2012-01-24
期刊：
影响因子：
--
通讯作者：
Linse S
中科院分区：
文献类型：
--
作者：
Cabaleiro-Lago C;Szczepankiewicz O;Linse S
纳米颗粒干扰蛋白淀粉样蛋白的形成。该过程的催化作用可能是由于纳米颗粒表面局部蛋白质浓度的增加和成核，而紧密结合或大颗粒/蛋白质表面积可能导致蛋白质聚集的抑制。在这里，我们展示了蛋白质固有稳定性和纳米粒子对聚集率的影响之间的明确相关性。这一结果是针对单链monellin在变性方面的内在稳定性不同的一系列5个突变体得出的，Szczepankiewicz等人先前已经记录了蛋白质稳定性与聚集倾向之间的相关性[Mol. biosyst2007(2), 521-532]。在不同疏水性质的共聚纳米粒子存在和不存在的情况下，利用硫黄素T荧光监测聚合过程。对于具有高内在稳定性和低内在聚集率的突变体，我们发现纳米颗粒加速了淀粉样蛋白纤维的形成。对于具有低内禀稳定性和高内禀聚集率的突变体，我们发现了相反的结果——纳米颗粒延缓了淀粉样蛋白纤维的形成。此外，疏水性最小的纳米颗粒具有更大的聚合物主链中氢键基团的表面可及性，其催化和抑制作用最为明显。
Nanoparticles interfere with protein amyloid formation. Catalysis of the process may occur due to increased local protein concentration and nucleation on the nanoparticle surface, whereas tight binding or a large particle/protein surface area may lead to inhibition of protein aggregation. Here we show a clear correlation between the intrinsic protein stability and the nanoparticle effect on the aggregation rate. The results were reached for a series of five mutants of single-chain monellin differing in intrinsic stability toward denaturation, for which a correlation between protein stability and aggregation propensity has been previously documented by Szczepankiewicz et al. [Mol. Biosyst.20107 (2), 521–532]. The aggregation process was monitored by thioflavin T fluorescence in the absence and presence of copolymeric nanoparticles with different hydrophobic characters. For mutants with a high intrinsic stability and low intrinsic aggregation rate, we find that amyloid fibril formation is accelerated by nanoparticles. For mutants with a low intrinsic stability and high intrinsic aggregation rate, we find the opposite—a retardation of amyloid fibril formation by nanoparticles. Moreover, both catalytic and inhibitory effects are most pronounced with the least hydrophobic nanoparticles, which have a larger surface accessibility of hydrogen-bonding groups in the polymer backbone.
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影响因子：
5
作者：
Cabaleiro-Lago, Celia;Quinlan-Pluck, Fiona;Linse, Sara
通讯作者：
Linse, Sara
DOI：
10.1038/nsb752
发表时间：
2002-02-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Chiti, F;Taddei, N;Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1073/pnas.212527999
发表时间：
2002-12-10
影响因子：
11.1
作者：
Chiti, F;Calamai, M;Dobson, CM
通讯作者：
Dobson, CM
影响因子：
13.8
作者：
Dobson, CM
通讯作者：
Dobson, CM
影响因子：
8
作者：
Konno, T
通讯作者：
Konno, T