Oxidative protein folding is driven by the electron transport system

Cell. 1999 Jul 23;98(2):217-27. doi: 10.1016/s0092-8674(00)81016-8.

Abstract

Disulfide bond formation is catalyzed in vivo by DsbA and DsbB. Here we reconstitute this oxidative folding system using purified components. We have found the sources of oxidative power for protein folding and show how disulfide bond formation is linked to cellular metabolism. We find that disulfide bond formation and the electron transport chain are directly coupled. DsbB uses quinones as electron acceptors, allowing various choices for electron transport to support disulfide bond formation. Electrons flow via cytochrome bo oxidase to oxygen under aerobic conditions or via cytochrome bd oxidase under partially anaerobic conditions. Under truly anaerobic conditions, menaquinone shuttles electrons to alternate final electron acceptors such as fumarate. This flexibility reflects the vital nature of the disulfide catalytic system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaerobiosis
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Catalytic Domain
  • Cytochrome b Group
  • Cytochromes / metabolism
  • DNA Primers
  • Disulfides / metabolism
  • Electron Transport / physiology*
  • Electron Transport Chain Complex Proteins*
  • Electron Transport Complex IV / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutagenesis / physiology
  • Oxidation-Reduction
  • Oxidoreductases / metabolism
  • Oxygen / analysis
  • Protein Disulfide-Isomerases / chemistry*
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism
  • Protein Folding*
  • Ubiquinone / metabolism

Substances

  • Bacterial Proteins
  • Cytochrome b Group
  • Cytochromes
  • DNA Primers
  • Disulfides
  • DsbB protein, Bacteria
  • Electron Transport Chain Complex Proteins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Ubiquinone
  • Oxidoreductases
  • cytochrome bd terminal oxidase complex, E coli
  • cytochrome o oxidase
  • Electron Transport Complex IV
  • Protein Disulfide-Isomerases
  • Oxygen