Structure of yeast cytochrome c oxidase in a supercomplex with cytochrome bc1

Cytochrome c oxidase (complex IV, CIV) is known in mammals to exist\ud independently or in association with other respiratory proteins to form\ud supercomplexes (SCs). In Saccharomyces cerevisiae, CIV is found solely in a\ud SC with cytochrome bc1 (complex III, CIII). Here, we present the cryo-EM\ud structure of S. cerevisiae CIV in a III2IV2 SC at 3.3 Å resolution. While overall\ud similarity to mammalian homologues is high, we found notable differences in\ud the supernumerary subunits Cox26 and Cox13; the latter exhibits a unique\ud arrangement that precludes CIV dimerization as seen in bovine. A\ud conformational shift in the matrix domain of Cox5A – involved in allosteric\ud inhibition by ATP – may arise from its association with CIII. The CIII–CIV\ud arrangement highlights a conserved interaction interface of CIII, albeit one\ud occupied by complex I in mammalian respirasomes. We discuss our findings\ud in the context of the potential impact of SC formation on CIV regulation