The small membrane protein CcoS is involved in cofactor insertion into the cbb3-type cytochrome c oxidase

Biochim Biophys Acta Bioenerg. 2025 Jan 1;1866(1):149524. doi: 10.1016/j.bbabio.2024.149524. Epub 2024 Nov 14.

Abstract

Respiratory complexes, such as cytochrome oxidases, are cofactor-containing multi-subunit protein complexes that are critically important for energy metabolism in all domains of life. Their intricate assembly strictly depends on accessory proteins, which coordinate subunit associations and cofactor deliveries. The small membrane protein CcoS was previously identified as an essential assembly factor to produce an active cbb3-type cytochrome oxidase (cbb3-Cox) in Rhodobacter capsulatus, but its function remained unknown. Here we show that the ΔccoS strain assembles a heme b deficient cbb3-Cox, in which the CcoN-CcoO subunit association is impaired. Chemical crosslinking demonstrates that CcoS interacts with the CcoN and CcoP subunits of cbb3-Cox, and that it stabilizes the interaction of the Cu-chaperone SenC with cbb3-Cox. CcoS lacks heme- or Cu-binding motifs, and we did not find evidence for direct heme or Cu binding; rather our data indicate that CcoS, together with SenC, coordinates heme and Cu insertion into cbb3-Cox.

Keywords: Cofactor insertion; Heme b; Rhodobacter capsulatus; SenC/ScoI; Small membrane proteins, respiration; cbb(3)-type cytochrome c oxidase.

MeSH terms

  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Copper* / metabolism
  • Electron Transport Complex IV* / chemistry
  • Electron Transport Complex IV* / genetics
  • Electron Transport Complex IV* / metabolism
  • Heme* / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Protein Binding
  • Rhodobacter capsulatus* / enzymology
  • Rhodobacter capsulatus* / genetics
  • Rhodobacter capsulatus* / metabolism

Substances

  • Electron Transport Complex IV
  • Bacterial Proteins
  • Copper
  • Heme
  • Membrane Proteins
  • cbb3 oxidase
  • Molecular Chaperones