Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA; Biological Chemistry Department, University of Michigan Medical School, Ann Arbor, MI, USA.
J Mol Biol. 2024 Jul 15;436(14):168504. doi: 10.1016/j.jmb.2024.168504. Epub 2024 Feb 27.
Inorganic polyphosphate (polyP), one of the first high-energy compound on earth, defies its extreme compositional and structural simplicity with an astoundingly wide array of biological activities across all domains of life. However, the underlying mechanism of such functional pleiotropy remains largely elusive. In this review, we will summarize recent studies demonstrating that this simple polyanion stabilizes protein folding intermediates and scaffolds select native proteins. These functions allow polyP to act as molecular chaperone that protects cells against protein aggregation, as pro-amyloidogenic factor that accelerates both physiological and disease-associated amyloid formation, and as a modulator of liquid-liquid phase separation processes. These activities help to explain polyP's known roles in bacterial stress responses and pathogenicity, provide the mechanistic foundation for its potential role in human neurodegenerative diseases, and open a new direction regarding its influence on gene expression through condensate formation. We will highlight critical unanswered questions and point out potential directions that will help to further understand the pleiotropic functions of this ancient and ubiquitous biopolymer.
无机多聚磷酸盐（polyP）是地球上最早的高能化合物之一，它的组成和结构极其简单，但在所有生命领域都具有惊人广泛的生物活性。然而，这种功能多样性的潜在机制在很大程度上仍然难以捉摸。在这篇综述中，我们将总结最近的研究表明，这种简单的多阴离子可以稳定蛋白质折叠中间体并支架选择天然蛋白质。这些功能使 polyP 能够充当分子伴侣，保护细胞免受蛋白质聚集的影响，作为促淀粉样蛋白形成的因素，加速生理和与疾病相关的淀粉样蛋白形成，以及作为液-液相分离过程的调节剂。这些活性有助于解释 polyP 在细菌应激反应和致病性中的已知作用，为其在人类神经退行性疾病中的潜在作用提供了机制基础，并开辟了一个关于其通过凝聚物形成影响基因表达的新方向。我们将重点介绍关键的未解决问题，并指出潜在的方向，这将有助于进一步了解这种古老而普遍的生物聚合物的多功能性。
