title: Polyphosphate is a primordial chaperone.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gray
authors.affiliation: 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.
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Wholey
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Nico O
authors.initials: NO
authors.lastname: Wagner
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Cremers
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Antje
authors.initials: A
authors.lastname: Mueller-Schickert
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Nathaniel T
authors.initials: NT
authors.lastname: Hock
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Krieger
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Smith
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bender
authors.affiliation: 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; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: James C A
authors.initials: JC
authors.lastname: Bardwell
authors.affiliation: 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. Electronic address: ujakob@umich.edu.
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
mesh_terms: D020134:Catalytic Domain; D002942:Circular Dichroism; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D008156:Luciferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D011122:Polyphosphates / Q000378:metabolism*; D011489:Protein Denaturation; D058767:Protein Unfolding; D013997:Time Factors
chemical_list: C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; C489400:GrpE protein, E coli; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011122:Polyphosphates; D008156:Luciferases; C063842:dnaK protein, E coli; D010100:Oxygen