Structure of the peripheral arm of a minimalistic respiratory complex I

Structure. 2022 Jan 6;30(1):80-94.e4. doi: 10.1016/j.str.2021.09.005. Epub 2021 Sep 24.

Abstract

Respiratory complex I drives proton translocation across energy-transducing membranes by NADH oxidation coupled with (ubi)quinone reduction. In humans, its dysfunction is associated with neurodegenerative diseases. The Escherichia coli complex represents the structural minimal form of an energy-converting NADH:ubiquinone oxidoreductase. Here, we report the structure of the peripheral arm of the E. coli complex I consisting of six subunits, the FMN cofactor, and nine iron-sulfur clusters at 2.7 Å resolution obtained by cryo electron microscopy. While the cofactors are in equivalent positions as in the complex from other species, individual subunits are adapted to the absence of supernumerary proteins to guarantee structural stability. The catalytically important subunits NuoC and D are fused resulting in a specific architecture of functional importance. Striking features of the E. coli complex are scrutinized by mutagenesis and biochemical characterization of the variants. Moreover, the arrangement of the subunits sheds light on the unknown assembly of the complex.

Keywords: Escherichia coli; NADH dehydrogenase; assembly; bioenergetics; complex I; cryo electron microscopy; electron transfer; iron-sulfur clusters; membrane proteins; quinones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Electron Transport Complex I / chemistry*
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation*
  • Protein Conformation
  • Protein Stability
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism

Substances

  • Escherichia coli Proteins
  • Protein Subunits
  • Electron Transport Complex I