Polyphosphate is a primordial chaperone

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Circular Dichroism
  • Drug Resistance, Bacterial
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • HSP40 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Luciferases / metabolism
  • Molecular Chaperones / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Oxygen / metabolism
  • Phenotype
  • Polyphosphates / metabolism*
  • Protein Denaturation
  • Protein Unfolding
  • Time Factors


  • DnaJ protein, E coli
  • Escherichia coli Proteins
  • GrpE protein, E coli
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Polyphosphates
  • Luciferases
  • dnaK protein, E coli
  • Oxygen