Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2023-11-01 DOI:10.1016/j.chemphyslip.2023.105350

Abid Ali , Kiryl Zhaliazka , Tianyi Dou , Aidan P. Holman , Dmitry Kurouski

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引用次数: 0

Abstract

Transthyretin (TTR) is a small, β-sheet-rich tetrameric protein that transports thyroid hormone thyroxine and retinol. Phospholipids, including phosphatidic acid (PA), can uniquely alter the stability of amyloidogenic proteins. However, the role of PA in TTR aggregation remains unclear. In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results shed light on the role of PA in the stability of TTR and transthyretin amyloidosis.

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磷脂酸中脂肪酸的饱和独特地改变了转甲状腺素的稳定性，改变了淀粉样原纤维的形态和毒性。

转甲状腺素（TTR）是一种小的、富含β片的四聚体蛋白，可转运甲状腺激素甲状腺素和视黄醇。磷脂，包括磷脂酸（PA），可以独特地改变淀粉样蛋白的稳定性。然而，PA在TTR聚集中的作用尚不清楚。在本研究中，我们研究了PA中脂肪酸饱和度（FA）对TTR聚集速率的影响。我们还揭示了具有不同长度和FA饱和度的PA在多大程度上改变了TTR聚集体的形态和二级结构。我们的结果表明，与在无脂环境中形成的原纤维相比，在等摩尔存在具有不同长度和FA饱和度的PA的情况下，TTR聚集产生了结构和形态不同的原纤维。我们还发现，PA显著降低了在这种磷脂存在下形成的TTR聚集体的毒性。这些结果阐明了PA在TTR和转甲状腺素淀粉样变性稳定性中的作用。

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

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.