Minimal structural perturbation of Histatin 5 in crowded environments: Insights from small-angle X-ray scattering, dynamic light scattering, and computer simulations

IF 9.4 1区 化学 Q1 CHEMISTRY, PHYSICAL
Eric Fagerberg , Peter Holmqvist , Samuel Lenton , Petra Pernot , Marie Skepö
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引用次数: 0

Abstract

The structure and dynamics of intrinsically disordered proteins (IDPs) are malleable to solution conditions. Considerable effort has been devoted to understanding the effects of molecular crowding on these properties. Polymer-based crowders, such as polyethylene glycol (PEG) and Ficoll®, are commonly used to simulate the intracellular environment by replicating the high concentration of macromolecules. In this study, we examine the impact of crowding on the IDP Histatin 5 using PEG of various molecular weights and Ficoll® PM 70. Small-angle X-ray scattering (SAXS) reveals minimal effects on the structural ensemble of Histatin 5 in the presence of both PEG and Ficoll® PM 70. These findings are further supported by dynamic light scattering (DLS) experiments, which confirm the SAXS results. However, as the molecular weight of PEG increases, the concentration at which the semidilute regime is reached decreases. A similar trend is observed for the larger crowder, Ficoll® PM 70. Computational models align with the experimental results, suggesting negligible crowding effects. Additionally, simulations indicate that the crowders undergo greater conformational changes with increasing concentration than Histatin 5. These findings support the idea that smaller IDPs, such as Histatin 5, could exhibit a rigid, rod-like conformation that makes them resistant to crowding effects.

Abstract Image

拥挤环境中组蛋白5的最小结构扰动:来自小角度x射线散射、动态光散射和计算机模拟的见解
内在无序蛋白(IDPs)的结构和动力学受到溶液条件的影响。在了解分子拥挤对这些性质的影响方面,已经付出了相当大的努力。聚合物基聚合剂,如聚乙二醇(PEG)和Ficoll®,通常用于通过复制高浓度的大分子来模拟细胞内环境。在本研究中,我们使用不同分子量的聚乙二醇和Ficoll®PM 70检测拥挤对IDP组蛋白5的影响。小角度x射线散射(SAXS)显示,PEG和Ficoll®PM 70存在时,对组蛋白5结构集合的影响很小。动态光散射(DLS)实验进一步证实了SAXS的结果。然而,随着PEG分子量的增加,达到半稀状态的浓度降低。类似的趋势也被观察到较大的蜂群,Ficoll®PM 70。计算模型与实验结果一致,表明拥挤效应可以忽略不计。此外,模拟表明,随着浓度的增加,crowders比组蛋白5发生更大的构象变化。这些发现支持了一种观点,即较小的IDPs,如组蛋白5,可能表现出刚性的棒状构象,使它们能够抵抗拥挤效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
16.10
自引率
7.10%
发文量
2568
审稿时长
2 months
期刊介绍: The Journal of Colloid and Interface Science publishes original research findings on the fundamental principles of colloid and interface science, as well as innovative applications in various fields. The criteria for publication include impact, quality, novelty, and originality. Emphasis: The journal emphasizes fundamental scientific innovation within the following categories: A.Colloidal Materials and Nanomaterials B.Soft Colloidal and Self-Assembly Systems C.Adsorption, Catalysis, and Electrochemistry D.Interfacial Processes, Capillarity, and Wetting E.Biomaterials and Nanomedicine F.Energy Conversion and Storage, and Environmental Technologies
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