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通过改变pH值调节酚溶性调节素的淀粉样蛋白样聚集动力学

Modulating Kinetics of the Amyloid-Like Aggregation of Phenol-Soluble Modulins by Changes in pH.

作者信息

Zaman Masihuz, Andreasen Maria

机构信息

Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.

出版信息

Microorganisms. 2021 Jan 7;9(1):117. doi: 10.3390/microorganisms9010117.

DOI:10.3390/microorganisms9010117
PMID:33430169
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7825627/
Abstract

The pathogen is recognized as one of the most frequent causes of biofilm-associated infections. The recently identified phenol-soluble modulin (PSM) peptides act as the key molecular effectors of staphylococcal biofilm maturation and promote the formation of an aggregated fibril structure. The aim of this study was to evaluate the effect of various pH values on the formation of functional amyloids of individual PSM peptides. Here, we combined a range of biophysical, chemical kinetics and microscopic techniques to address the structure and aggregation mechanism of individual PSMs under different conditions. We established that there is a pH-induced switch in PSM aggregation kinetics. Different lag times and growth of fibrils were observed, which indicates that there was no clear correlation between the rates of fibril elongation among different PSMs. This finding confirms that pH can modulate the aggregation properties of these peptides and suggest a deeper understanding of the formation of aggregates, which represents an important basis for strategies to interfere and might help in reducing the risk of biofilm-related infections.

摘要

该病原体被认为是生物膜相关感染最常见的病因之一。最近鉴定出的酚溶性调节蛋白(PSM)肽是葡萄球菌生物膜成熟的关键分子效应物,并促进聚集纤维结构的形成。本研究的目的是评估不同pH值对单个PSM肽功能性淀粉样蛋白形成的影响。在这里,我们结合了一系列生物物理、化学动力学和显微镜技术,以研究不同条件下单个PSM的结构和聚集机制。我们确定PSM聚集动力学存在pH诱导的转变。观察到不同的延迟时间和纤维生长情况,这表明不同PSM之间的纤维伸长率没有明显的相关性。这一发现证实pH可以调节这些肽的聚集特性,并提示对聚集体形成有更深入的理解,这是干扰策略的重要基础,可能有助于降低生物膜相关感染的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d330/7825627/cf2e2c0df2ef/microorganisms-09-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d330/7825627/cf2e2c0df2ef/microorganisms-09-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d330/7825627/cf2e2c0df2ef/microorganisms-09-00117-g001.jpg

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Functional Amyloids.功能性淀粉样蛋白
Cold Spring Harb Perspect Biol. 2019 Dec 2;11(12):a033860. doi: 10.1101/cshperspect.a033860.
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pH-Dependent fibril maturation of a Pmel17 repeat domain isoform revealed by tryptophan fluorescence.色氨酸荧光法揭示 pH 依赖性 Pmel17 重复结构域异构体原纤维成熟
超越一招鲜:微生物功能性淀粉样蛋白的多功能奇迹
Microorganisms. 2023 May 4;11(5):1201. doi: 10.3390/microorganisms11051201.
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Functional amyloids from bacterial biofilms - structural properties and interaction partners.来自细菌生物膜的功能性淀粉样蛋白——结构特性与相互作用伙伴
Chem Sci. 2022 May 6;13(22):6457-6477. doi: 10.1039/d2sc00645f. eCollection 2022 Jun 7.
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