Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Cell. 2014 Mar 6;53(5):689-99. doi: 10.1016/j.molcel.2014.01.012. Epub 2014 Feb 20.
Composed of up to 1,000 phospho-anhydride bond-linked phosphate monomers, inorganic polyphosphate (polyP) is one of the most ancient, conserved, and enigmatic molecules in biology. Here we demonstrate that polyP functions as a hitherto unrecognized chaperone. We show that polyP stabilizes proteins in vivo, diminishes the need for other chaperone systems to survive proteotoxic stress conditions, and protects a wide variety of proteins against stress-induced unfolding and aggregation. In vitro studies reveal that polyP has protein-like chaperone qualities, binds to unfolding proteins with high affinity in an ATP-independent manner, and supports their productive refolding once nonstress conditions are restored. Our results uncover a universally important function for polyP and suggest that these long chains of inorganic phosphate may have served as one of nature's first chaperones, a role that continues to the present day.
由多达 1000 个磷酸酐键连接的磷酸单体组成，无机多聚磷酸盐（polyP）是生物学中最古老、最保守、最神秘的分子之一。在这里，我们证明了 polyP 作为一种迄今为止尚未被认识的伴侣蛋白发挥作用。我们表明，polyP 在体内稳定蛋白质，减少了其他伴侣蛋白系统在应对蛋白毒性应激条件下生存的需要，并保护各种蛋白质免受应激诱导的解折叠和聚集。体外研究表明，polyP 具有类似蛋白质的伴侣蛋白特性，以非 ATP 依赖的方式与展开的蛋白质高亲和力结合，并在非应激条件恢复后支持它们的有效重折叠。我们的结果揭示了 polyP 的普遍重要功能，并表明这些长链无机磷酸盐可能曾经是自然界最早的伴侣蛋白之一，这种作用一直持续到今天。
