Building the CuA site of cytochrome c oxidase: A complicated, redox-dependent process driven by a surprisingly large complement of accessory proteins

J Biol Chem. 2018 Mar 30;293(13):4644-4652. doi: 10.1074/jbc.R117.816132. Epub 2017 Sep 29.

Abstract

Cytochrome c oxidase (COX) was initially purified more than 70 years ago. A tremendous amount of insight into its structure and function has since been gleaned from biochemical, biophysical, genetic, and molecular studies. As a result, we now appreciate that COX relies on its redox-active metal centers (heme a and a3, CuA and CuB) to reduce oxygen and pump protons in a reaction essential for most eukaryotic life. Questions persist, however, about how individual structural subunits are assembled into a functional holoenzyme. Here, we focus on what is known and what remains to be learned about the accessory proteins that facilitate CuA site maturation.

Keywords: COX assembly factors; CuA site formation; chaperone; copper; cytochrome c oxidase (complex IV); mitochondria; protein assembly.

Publication types

  • Review

MeSH terms

  • Catalytic Domain
  • Copper* / chemistry
  • Copper* / metabolism
  • Electron Transport Complex IV* / biosynthesis
  • Electron Transport Complex IV* / chemistry
  • Heme / analogs & derivatives*
  • Heme / chemistry
  • Heme / metabolism
  • Ion Transport / physiology
  • Oxygen / chemistry
  • Oxygen / metabolism
  • Protein Subunits* / chemistry
  • Protein Subunits* / metabolism
  • Protons

Substances

  • Protein Subunits
  • Protons
  • heme a
  • Heme
  • Copper
  • Electron Transport Complex IV
  • Oxygen