STRUCTURE OF THE MITOCHONDRIAL CYTOCHROME C REDUCTASE: A BIFUNCTIONAL MEMBRANE PROTEIEN COMPLEX

So Iwata

Uppsala University, Department of Biochemistry, BMC, S-75123, Uppsala, Sweden.

The first crystal structure of the entire 11-subunit cytochrome bc1 complex from bovine heart has been determined. All subunits are well defined and more than 97% of the sequence of the bovine enzyme complex have been fitted to the electron density map. The structure was solved using two different crystal forms of space group P6522 and P65; these crystals diffract up to 3.0 and 2.8 A respectively. The initial MIR phase has been determined for the P6522 crystal form at 4 A resolution and was followed by multi-crystal averaging to extend the phase out to 3.0 A resolution. This provided clear, easily fittable densities which afforded a good working model of the complex. Atomic details for the arrangement of the four redox centers and the two quinone binding sites have been well determined. These structural details, together with the observed structural differences of the Rieske protein in the two different crystal forms, suggest a mechanism by which electron transfer is coupled to proton translocation in the bc1 complex. Furthermore, an interesting neighboring association of one of the subunits, which happens to be the mitochondrial targeting presequence of the Rieske protein (subunit 9), provides a suggestion as to how cellular proteins are targeted to the mitochondria.