首页> 外文期刊>The Journal of biological chemistry >Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol
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Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol

机译:在三氟乙醇中超声显着增强的原纤蛋白淀粉样蛋白淀粉样蛋白原纤维的多态性

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The polymorphic property of amyloid structures has been focused on as a molecular basis of the presence and propagation of different phenotypes of amyloid diseases, although little is known about the molecular mechanism for expressing diverse structures from only one protein sequence. Here, we have found that, in combination with an enhancing effect of ultrasonication on nucleation, β2-microglobulin, a protein responsible for dialysis-related amyloidosis, generates distinct fibril conformations in a concentration-dependent manner in the presence of 2,2,2-trifluoroethanol (TFE). Although the newly formed fibrils all exhibited a similar needle-like morphology with an extensive cross-β core, as suggested by Fourier transform infrared absorption spectra, they differed in thioflavin T intensity, extension kinetics, and tryptophan fluorescence spectra even in the same solvents, representing polymorphic structures. The hydrophobic residues seemed to be more exposed in the fibrils originating at higher concentrations of TFE, as indicated by the increased binding of 1-anilinonaphthalene-8-sulfonic acid, suggesting that the modulation of hydrophobic interactions is critical to the production of polymorphic amyloid structures. Interestingly, the fibrils formed at higher TFE concentrations showed significantly higher stability against guanidium hydrochloride, the perturbation of ionic strength, and, furthermore, pressurization. The cross-β structure inside the fibrils seems to have been more idealized, resulting in increased stability when nucleation occurred in the presence of the alcohol, indicating that a weaker contribution of hydrophobic interactions is intrinsically more amenable to the formation of a non-defective amyloid structure.
机译:淀粉样蛋白结构的多晶型特性以淀粉样蛋白疾病的不同表型的存在和繁殖的分子基础集中于淀粉样蛋白疾病的存在和繁殖的分子基础。虽然关于从只有一种蛋白质序列表达不同结构的分子机制很少。在这里,我们发现,结合超声波对成核的增强作用,β2-微球蛋白,负责透析相关淀粉样蛋白病的蛋白质,在2,2,2的存在下以浓度依赖性方式产生不同的原纤维符合 - 氟乙醇(TFE)。虽然新形成的原纤维均表现出类似的针状形态,但是由于傅里叶变换红外吸收光谱,它们在硫蛋白T强度,延长动力学和色氨酸荧光光谱中的不同,虽然表现出具有广泛的交叉β核,但即使在相同的溶剂中,则在硫蛋白T强度,延长动力学和色氨酸荧光光谱。代表多态结构。疏水残留似乎更暴露于源自较高浓度TFE的原纤维中,如1-苯胺萘-8-磺酸的增加所示,表明疏水性相互作用的调节对于生产多态淀粉样蛋白结构至关重要。有趣的是,在较高的TFE浓度下形成的原纤维显示出对盐酸胍的稳定性显着较高,离子强度的扰动,以及加压。原纤维内的十字β结构似乎更加理想,导致在醇的存在下发生成核时的稳定性增加,表明疏水性相互作用的较弱贡献本质上更常用于形成无缺陷淀粉样蛋白结构体。

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