Thermal stability of bivalent cation/phosphoinositide domains in model membranes

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Trevor A. Paratore, Greta E. Schmidt, Alonzo H. Ross, Arne Gericke
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引用次数: 0

Abstract

As key mediators in a wide array of signaling events, phosphoinositides (PIPs) orchestrate the recruitment of proteins to specific cellular locations at precise moments. This intricate spatiotemporal regulation of protein activity often necessitates the localized enrichment of the corresponding PIP. We investigate the extent and thermal stabilities of phosphatidylinositol-4-phosphate (PI(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2 and phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) clusters with calcium and magnesium ions. We observe negligible or minimal clustering of all examined PIPs in the presence of Mg2+ ions. While PI(4)P shows in the presence of Ca2+ no clustering, PI(4,5)P2 forms with Ca2+ strong clusters that exhibit stablity up to at least 80°C. The extent of cluster formation for the interaction of PI(3,4,5)P3 with Ca2+ is less than what was observed for PI(4,5)P2, yet we still observe some clustering up to 80°C. Given that cholesterol has been demonstrated to enhance PIP clustering, we examined whether bivalent cations and cholesterol synergistically promote PIP clustering. We found that the interaction of Mg2+ or Ca2+ with PI(4)P remains extraordinarily weak, even in the presence of cholesterol. In contrast, we observe synergistic interaction of cholesterol and Ca2+ with PI(4,5)P2. Also, in the presence of cholesterol, the interaction of Mg2+ with PI(4,5)P2 remains weak. PI(3,4,5)P3 does not show strong clustering with cholesterol for the experimental conditions of our study and the interaction with Ca2+ and Mg2+ was not influenced by the presence of cholesterol.

模型膜中二价阳离子/磷酸肌酸结构域的热稳定性。
磷酸肌酸(PIPs)是一系列信号传导事件的关键媒介,它能在精确的时刻将蛋白质招募到特定的细胞位置。这种错综复杂的蛋白质活性时空调控往往要求相应的 PIP 在局部富集。我们研究了磷脂酰肌醇-4-磷酸(PI(4)P)、磷脂酰肌醇-4,5-二磷酸(PI(4,5)P2)和磷脂酰肌醇-3,4,5-三磷酸(PI(3,4,5)P3)与钙离子和镁离子成簇的程度和热稳定性。我们观察到,在 Mg2+ 离子存在的情况下,所有检测到的 PIP 聚类都可以忽略不计或微乎其微。PI(4)P在钙离子存在时不形成团簇,而PI(4,5)P2与钙离子形成的强团簇至少在 80°C 时仍保持稳定。PI(3,4,5)P3与 Ca2+ 相互作用形成团簇的程度小于 PI(4,5)P2 观察到的程度,但我们仍然观察到一些团簇(温度可达 80°C)。鉴于胆固醇已被证明能增强 PIP 聚类,我们研究了二价阳离子和胆固醇是否能协同促进 PIP 聚类。我们发现,即使在胆固醇存在的情况下,Mg2+ 或 Ca2+ 与 PI(4)P 的相互作用仍然异常微弱。相反,我们观察到胆固醇和 Ca2+ 与 PI(4,5)P2 的协同作用。此外,在胆固醇存在的情况下,Mg2+ 与 PI(4,5)P2 的相互作用仍然很弱。在我们研究的实验条件下,PI(3,4,5)P3 与胆固醇的聚类作用并不强,与 Ca2+ 和 Mg2+ 的相互作用不受胆固醇存在的影响。
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来源期刊
Chemistry and Physics of Lipids
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
50
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.
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