Structure and reaction mechanisms of multifunctional mitochondrial cytochrome bc₁ complex

The cytochrome bc₁ complex from bovine heart mitochondria is a multi- functional enzyme complex. In addition to electron and proton transfer activity, the complex also processes an activatable peptidase activity and a superoxide generating activity. The crystal structure of the complex exists as a closely interacting functional dimer. There are 13 transmembrane helices in each monomer, eight of which belong to cytochrome b, and five of which belong to cytochrome c₁, Rieske iron-sulfur protein (ISP), subunits 7, 10 and 11, one each. The distances of 21 Å between b(L) heme and b(H) heme and of 27 Å. between b(L) heme and the iron-sulfur cluster (FeS), accommodate well the observed fast electron transfers between the involved redox centers. However, the distance of 31 Å between heme c₁ and FeS, makes it difficult to explain the high electron transfer rate between them. 3D structural analyses of the bc₁ complexes co-crystallized with the Q₀ site inhibitors suggest that the extramembrane domain of the ISP may undergo substantial movement during the catalytic cycle of the complex. This suggestion is further supported by the decreased in the cytochrome bc₁ complex activity and the increased in activation energy for mutants with increased rigidity in the neck region of ISP.