Polyphosphate Is a Primordial Chaperone

• Published in: Molecular cell Vol. 53; no. 5; pp. 689 - 699
• Main Authors: Gray, Michael J., Wholey, Wei-Yun, Wagner, Nico O., Cremers, Claudia M., Mueller-Schickert, Antje, Hock, Nathaniel T., Krieger, Adam G., Smith, Erica M., Bender, Robert A., Bardwell, James C.A., Jakob, Ursula
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.03.2014
• Subjects: Catalytic Domain; Circular Dichroism; Drug Resistance, Bacterial; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Heat-Shock Proteins - metabolism; Hot Temperature; HSP40 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - metabolism; Luciferases - metabolism; Molecular Chaperones - metabolism; Oxidation-Reduction; Oxidative Stress; Oxygen - metabolism; Phenotype; Polyphosphates - metabolism; Protein Denaturation; Protein Unfolding; Time Factors
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2014.01.012

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. [Display omitted] •Polyphosphate protects against proteotoxic oxidative stress conditions•Polyphosphate is a prebiotic and universally conserved molecular chaperone•Different-length polyphosphates differ in their chaperone efficacies•Polyphosphate accumulation is mediated by the redox-regulated enzyme PPX Studies of bacterial resistance to proteotoxic stress reveal that inorganic polyphosphate functions as a chaperone, stabilizing unfolding proteins and preventing aggregation. Here, Gray et al. help uncover polyphosphate’s long known but largely unexplained role in protecting organisms against stress, and suggest that polyP may have served as one of nature’s first chaperones.