Structural basis of multifunctional bovine mitochondrial cytochrome bc1 complex.
The mitochondrial cytochrome bc1 complex is a multifunctional membrane protein complex. It catalyzes electron transfer, proton translocation, peptide processing, and superoxide generation. Crystal structure data at 2.9 A resolution not only establishes the location of the redox centers and inhibitor binding sites, but also suggests a movement of the head domain of the iron-sulfur protein (ISP) during bc1 catalysis and inhibition of peptide-processing activity during complex maturation. The functional importance of the movement of extramembrane (head) domain of ISP in the bc1 complex is confirmed by analysis of the Rhodobacter sphaeroides bc1 complex mutants with increased rigidity in the ISP neck and by the determination of rate constants for acid/base-induced intramolecular electron transfer between [2Fe-2S] and heme c1 in native and inhibitor-loaded beef complexes. The peptide-processing activity is activated in bovine heart mitochondrial bc1 complex by nonionic detergent at concentrations that inactivate electron transfer activity. This peptide-processing activity is shown to be associated with subunits I and II by cloning, overexpression and in vitro reconstitution. The superoxide-generation site of the cytochrome bc1 complex is located at reduced bL and Q*-. The reaction is membrane potential-, and cytochrome c-dependent.
Yu
C A
CA
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater 74078-3035, USA. cayuq@okway.okstate.edu
Tian
H
H
Zhang
L
L
Deng
K P
KP
Shenoy
S K
SK
Yu
L
L
Xia
D
D
Kim
H
H
Deisenhofer
J
J
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D001665:Binding Sites; D002417:Cattle; D003460:Crystallization; D018360:Crystallography, X-Ray; D003902:Detergents / Q000494:pharmacology; D019281:Dimerization; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D012242:Rhodobacter sphaeroides / Q000201:enzymology; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000737:chemistry
D001426:Bacterial Proteins; D003902:Detergents; D007506:Iron-Sulfur Proteins; D011522:Protons; C037989:Rieske iron-sulfur protein; D013481:Superoxides; D014451:Ubiquinone; D007501:Iron; D014450:Electron Transport Complex III