Structure of the intact 14-subunit human cytochrome c oxidase

Cell Res. 2018 Oct;28(10):1026-1034. doi: 10.1038/s41422-018-0071-1. Epub 2018 Jul 20.

Abstract

Respiration is one of the most basic features of living organisms, and the electron transport chain complexes are probably the most complicated protein system in mitochondria. Complex-IV is the terminal enzyme of the electron transport chain, existing either as randomly scattered complexes or as a component of supercomplexes. NDUFA4 was previously assumed as a subunit of complex-I, but recent biochemical data suggested it may be a subunit of complex-IV. However, no structural evidence supporting this notion was available till now. Here we obtained the 3.3 Å resolution structure of complex-IV derived from the human supercomplex I1III2IV1 and assigned the NDUFA4 subunit into complex-IV. Intriguingly, NDUFA4 lies exactly at the dimeric interface observed in previously reported crystal structures of complex-IV homodimer which would preclude complex-IV dimerization. Combining previous structural and biochemical data shown by us and other groups, we propose that the intact complex-IV is a monomer containing 14 subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Dimerization
  • Electron Transport Complex IV / chemistry*
  • Electron Transport Complex IV / isolation & purification
  • Electron Transport Complex IV / metabolism
  • HEK293 Cells
  • Humans
  • Mitochondria / metabolism
  • Molecular Docking Simulation
  • Myocardium / metabolism
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protein Subunits / isolation & purification
  • Protein Subunits / metabolism
  • Swine

Substances

  • Protein Subunits
  • Electron Transport Complex IV
  • NDUFA4 protein, human