NMR solution structure of the integral membrane enzyme DsbB: functional insights into DsbB-catalyzed disulfide bond formation

Mol Cell. 2008 Sep 26;31(6):896-908. doi: 10.1016/j.molcel.2008.08.028.


We describe the NMR structure of DsbB, a polytopic helical membrane protein. DsbB, a bacterial cytoplasmic membrane protein, plays a key role in disulfide bond formation. It reoxidizes DsbA, the periplasmic protein disulfide oxidant, using the oxidizing power of membrane-embedded quinones. We determined the structure of an interloop disulfide bond form of DsbB, an intermediate in catalysis. Analysis of the structure and interactions with substrates DsbA and quinone reveals functionally relevant changes induced by these substrates. Analysis of the structure, dynamics measurements, and NMR chemical shifts around the interloop disulfide bond suggest how electron movement from DsbA to quinone through DsbB is regulated and facilitated. Our results demonstrate the extraordinary utility of NMR for functional characterization of polytopic integral membrane proteins and provide insights into the mechanism of DsbB catalysis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Catalysis
  • Cell Membrane / enzymology*
  • Cysteine / metabolism
  • Disulfides / metabolism*
  • Electron Spin Resonance Spectroscopy
  • Escherichia coli / cytology*
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry
  • Lipid Bilayers / metabolism
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Oxidation-Reduction
  • Periplasm / enzymology
  • Protein Disulfide-Isomerases / chemistry
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Solutions
  • Ubiquinone


  • Bacterial Proteins
  • Disulfides
  • DsbB protein, Bacteria
  • Escherichia coli Proteins
  • Lipid Bilayers
  • Membrane Proteins
  • Solutions
  • Ubiquinone
  • Protein Disulfide-Isomerases
  • dsbA protein, E coli
  • Cysteine

Associated data

  • PDB/2K73
  • PDB/2K74