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PMID: 24560923 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Polyphosphate is a primordial chaperone.

Molecular cell ·Vol. 53 ·No. 5 ·2014-03-06 ·Pages 689-99

Gray MJ, Wholey WY, Wagner NO, Cremers CM, Mueller-Schickert A, Hock NT, Krieger AG, Smith EM, Bender RA, Bardwell JC, Jakob U

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.

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
Chemicals
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
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Gray Michael J
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Wholey Wei-Yun
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.
Wagner Nico O
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Cremers Claudia M
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Mueller-Schickert Antje
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.
Hock Nathaniel T
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Krieger Adam G
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Smith Erica M
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Bender Robert A
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Bardwell James C A
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.
Jakob Ursula
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.
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2014.01.012
Email
ujakob@umich.edu
Published
2014-03-06
Epub
2014-00-20
Pages
689-99
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3996911
Subset
IM
Grants
NIGMS NIH HHS · F32-GM096613 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · AI097893 · United States
NIGMS NIH HHS · T32-GM007315 · United States
NIGMS NIH HHS · F32 GM096613 · United States
NIGMS NIH HHS · R01 GM065318 · United States
NIAID NIH HHS · R21 AI097893 · United States
NIGMS NIH HHS · GM065318 · United States
NIGMS NIH HHS · T32 GM007315 · United States
Corrections
CommentIn
PMID: 24606917
External Links
PubMed source DOI: 10.1016/j.molcel.2014.01.012 PMC Full Text View journal details
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