Structure of an Ancient Respiratory System

Cell. 2018 Jun 14;173(7):1636-1649.e16. doi: 10.1016/j.cell.2018.03.071. Epub 2018 May 10.


Hydrogen gas-evolving membrane-bound hydrogenase (MBH) and quinone-reducing complex I are homologous respiratory complexes with a common ancestor, but a structural basis for their evolutionary relationship is lacking. Here, we report the cryo-EM structure of a 14-subunit MBH from the hyperthermophile Pyrococcus furiosus. MBH contains a membrane-anchored hydrogenase module that is highly similar structurally to the quinone-binding Q-module of complex I while its membrane-embedded ion-translocation module can be divided into a H+- and a Na+-translocating unit. The H+-translocating unit is rotated 180° in-membrane with respect to its counterpart in complex I, leading to distinctive architectures for the two respiratory systems despite their largely conserved proton-pumping mechanisms. The Na+-translocating unit, absent in complex I, resembles that found in the Mrp H+/Na+ antiporter and enables hydrogen gas evolution by MBH to establish a Na+ gradient for ATP synthesis near 100°C. MBH also provides insights into Mrp structure and evolution of MBH-based respiratory enzymes.

Keywords: Mrp antiporter; cation/proton antiporter; complex I; cryo-EM; hydrogen gas; hydrogenase; membrane protein; protein structure; respiration evolution of respiratory complexes; structural biology.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cryoelectron Microscopy
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / metabolism
  • Evolution, Molecular
  • Hydrogen / metabolism
  • Hydrogenase / chemistry
  • Hydrogenase / genetics
  • Hydrogenase / metabolism*
  • Mutagenesis
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Pyrococcus furiosus / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Sequence Alignment
  • Sodium / chemistry
  • Sodium / metabolism
  • Sodium-Hydrogen Exchangers / chemistry
  • Sodium-Hydrogen Exchangers / metabolism


  • Archaeal Proteins
  • Bacterial Proteins
  • Protein Subunits
  • Recombinant Proteins
  • Sodium-Hydrogen Exchangers
  • Hydrogen
  • Sodium
  • Hydrogenase
  • Electron Transport Complex I