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The inhibition of fibril formation of lysozyme by sucrose and trehalose
RSC Advances ( IF 3.9 ) Pub Date : 2024-04-15 , DOI: 10.1039/d4ra01171f
Kajsa Ahlgren 1 , Fritjof Havemeister 2 , Julia Andersson 1 , Elin K. Esbjörner 2 , Jan Swenson 1
Affiliation  

The two disaccharides, trehalose and sucrose, have been compared in many studies due to their structural similarity. Both possess the ability to stabilise and reduce aggregation of proteins. Trehalose has also been shown to inhibit the formation of highly structured protein aggregates called amyloid fibrils. This study aims to compare how the thermal stability of the protein lysozyme at low pH (2.0 and 3.5) is affected by the presence of the two disaccharides. We also address the anti-aggregating properties of the disaccharides and their inhibitory effects on fibril formation. Differential scanning calorimetry confirms that the thermal stability of lysozyme is increased by the presence of trehalose or sucrose. The effect is slightly larger for sucrose. The inhibiting effects on protein aggregation are investigated using small-angle X-ray scattering which shows that the two-component system consisting of lysozyme and water (Lys/H2O) at pH 2.0 contains larger aggregates than the corresponding system at pH 3.5 as well as the sugar containing systems. In addition, the results show that the particle-to-particle distance in the sugar containing systems (Lys/Tre/H2O and Lys/Suc/H2O) at pH 2.0 is longer than at pH 3.5, suggesting larger protein aggregates in the former. Finally, the characteristic distance separating β-strands in amyloid fibrils is observed for the Lys/H2O system at pH 2.0, using wide-angle X-ray scattering, while it is not clearly observed for the sugar containing systems. This study further shows that the two disaccharides stabilise the native fold of lysozyme by increasing the denaturation temperature. However, other factors, such as a weakening of hydrophobic interactions and hydrogen bonding between proteins, might also play a role in their inhibitory effect on amyloid fibril formation.

中文翻译:

蔗糖和海藻糖对溶菌酶原纤维形成的抑制作用

海藻糖和蔗糖这两种二糖由于结构相似,在许多研究中进行了比较。两者都具有稳定和减少蛋白质聚集的能力。海藻糖还被证明可以抑制称为淀粉样原纤维的高度结构化蛋白质聚集体的形成。本研究旨在比较两种二糖的存在如何影响蛋白质溶菌酶在低 pH(2.0 和 3.5)下的热稳定性。我们还研究了二糖的抗聚集特性及其对原纤维形成的抑制作用。差示扫描量热法证实海藻糖或蔗糖的存在增加了溶菌酶的热稳定性。蔗糖的影响稍大一些。使用小角 X 射线散射研究了对蛋白质聚集的抑制作用,结果表明,pH 2.0 时由溶菌酶和水 (Lys/H 2 O) 组成的双组分系统比 pH 3.5 时的相应系统包含更大的聚集体,如下所示:以及含糖系统。此外,结果表明,含糖系统(Lys/Tre/H 2 O 和 Lys/Suc/H 2 O)中的颗粒间距离在 pH 2.0 时比在 pH 3.5 时更长,表明存在较大的蛋白质聚集体在前者。最后,使用广角 X 射线散射,在 pH 2.0 的Lys/H 2 O 系统中观察到了淀粉样原纤维中 β 链分隔的特征距离,而在含糖系统中则没有清楚地观察到这一点。这项研究进一步表明,这两种二糖通过提高变性温度来稳定溶菌酶的天然折叠。然而,其他因素,例如蛋白质之间疏水相互作用和氢键的减弱,也可能在它们对淀粉样原纤维形成的抑制作用中发挥作用。
更新日期:2024-04-15
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