Crystal Structure of the Cytochrome bc ₁ Complex from Bovine Heart Mitochondria

Abstract

On the basis of x-ray diffraction data to a resolution of 2.9 angstroms, atomic models of most protein components of the bovine cytochrome bc1 complex were built, including core 1, core 2, cytochrome b, subunit 6, subunit 7, a carboxyl-terminal fragment of cytochrome c1, and an amino-terminal fragment of the iron-sulfur protein. The positions of the four iron centers within the bc1 complex and the binding sites of the two specific respiratory inhibitors antimycin A and myxothiazol were identified. The membrane-spanning region of each bc1 complex monomer consists of 13 transmembrane helices, eight of which belong to cytochrome b. Closely interacting monomers are arranged as symmetric dimers and form cavities through which the inhibitor binding pockets can be accessed. The proteins core 1 and core 2 are structurally similar to each other and consist of two domains of roughly equal size and identical folding topology.

A structural moDAl for the membrane‐integral domain of succinate:quinone oxidoreductases

“…In quinol:-cytochrome c reductase the two heroes are ligated by only two transmembrane helices; each pair of histidines on the two helices are 13 14 residues apart. As a consequence, the two hemes are approximately oriented in the same plane and positioned at a fixed distance, 20 A, [5], from each other. In the diheme succinate:quinone oxidoreductases the relative position of the two hemes can be more flexible.…”

“…SQR in many organisms contains cytochrome of b-type [1,2]. The function and structure of this cytochrome is poorly understood as compared to that of the cytochrome bc/bf (complex III, quinol:cytochrome c reductase) and cytochrome c oxidase (complex IV) [3][4][5].…”

X-Ray Structure of Rhodobacter Capsulatus Cytochrome bc1: Comparison with its Mitochondrial and Chloroplast Counterparts

“…Indeed, a great deal of information is available concerning the effects of single, as well as compensatory pairs of point mutations on the assembly and function of Rhodobacter cyt bc 1 (Brasseur et al 1996). While the interpretation of these data has been greatly aided by the availability of the mitochondrial structures (Xia et al 1997;Iwata et al 1998;Zhang et al 1998;Hunte et al 2000;Gao et al 2003;Palsdottir et al 2003), there are also important differences due to specific insertions and deletions that are uniquely present in the bacterial or mitochondrial enzymes.…”

“…Various three dimensional structures of the mitochondrial cyt bc 1 , which have been accumulated during the last several years (Xia et al 1997;Iwata et al 1998;Zhang et al 1998;Hunte et al 2000;Gao et al 2003;Palsdottir et al 2003), have recently been supplemented by the structures of the cyt b 6 f from cyanobacteria and chloroplast (Kurisu et al 2003;Stroebel et al 2003). Crystallization of the simpler bacterial cyt bc 1 has been 6 considerably more challenging, and the crystals obtained to date are not particularly satisfactory for structure determination due to high mosaicity as well as poor and anisotropic crystalline order.…”

Napyradiomycin A1, an inhibitor of mitochondrial complexes I and II

“…12 Napyradiomycin A1 is structurally similar to ubiquinone ( Figure 1a); therefore, it is likely that napyradiomycin A1 binds with the ubiquinone-binding site of complexes I and II through its terpenoid residue. On the other hand, although mitochondrial complex III also includes a ubiquinone-binding site, 13 napyradiomycin A1 was unable to inhibit the activity of complex III up to 20 mM. Our result that napyradiomycin A1 inhibits mitochondrial complexes I and II but not complex III is interesting, because it has been reported that the structure of ubiquinone-binding sites in complex I and complex III may be similar, but they are different from a ubiquinone-binding site in complex II.…”