Structure of the peripheral arm of a minimalistic respiratory complex I

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 angstrom 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.

Automated summary

Respiratory complex I drives proton translocation across energy-transducing membranes by oxidizing NADH and reducing (ubi)quinone. The structure of the peripheral arm of the E coli complex I has been determined, consisting of six subunits, FMN cofactor, and nine iron-sulfur clusters, using cryo electron microscopy. The fusion of catalytically important subunits in E. coli complex I results in a specific architecture of functional importance. Mutagenesis and biochemical characterization of variants have provided insights into the features of the E. coli complex and shed light on its unknown assembly.