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首页> 外文期刊>Chemistry: A European journal >Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues
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Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues

机译：细胞阳离子控制肌醇焦磷酸类似物的构象转换

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The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.
机译：肌醇焦磷酸盐信使（PP-InsPs）逐渐成为一类重要的细胞调节剂。这些分子与许多生物过程有关，包括胰岛素分泌和癌细胞迁移，但是在许多情况下，它们如何触发如此广泛的细胞反应仍未得到解答。在这里，我们表明PP-InsPs表现出复杂的物种形成行为，并提出独特的构象转换机制可能有助于其多功能作用。我们合成了不可水解的双膦酸酯类似物，并与哺乳动物PPIP5K2激酶复合后结晶了类似物。随后，使用双膦酸酯类似物研究溶液中的质子化序列，金属配位性质和构象。值得注意的是，钾和镁离子的存在使类似物在生理pH值附近具有两种不同的构象。了解PP-InsP的内在化学特性如何有助于其复杂的信号输出对于阐明其调节功能至关重要。

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