Crystal structure of the yeast cytochrome bc ₁ complex with its bound substrate cytochrome c

Abstract

Small diffusible redox proteins facilitate electron transfer in respiration and photosynthesis by alternately binding to integral membrane proteins. Specific and transient complexes need to be formed between the redox partners to ensure fast turnover. In respiration, the mobile electron carrier cytochrome c shuttles electrons from the cytochrome bc 1 complex to cytochrome c oxidase. Despite extensive studies of this fundamental step of energy metabolism, the structures of the respective electron transfer complexes were not known. Here we present the crystal structure of the complex between cytochrome c and the cytochrome bc 1 complex from Saccharomyces cerevisiae. The complex was crystallized with the help of an antibody fragment, and its structure was determined at 2.97-Å resolution. Cytochrome c is bound to subunit cytochrome c 1 of the enzyme. The tight and specific interactions critical for electron transfer are mediated mainly by nonpolar forces. The close spatial arrangement of the c-type hemes unexpectedly suggests a direct and rapid heme-to-heme electron transfer at a calculated rate of up to 8.3 ؋ 10 6 s ؊1 . Remarkably, cytochrome c binds to only one recognition site of the homodimeric multisubunit complex. Interestingly, the occupancy of quinone in the Qi site is higher in the monomer with bound cytochrome c, suggesting a coordinated binding and reduction of both electron-accepting substrates. Obviously, cytochrome c reduction by the cytochrome bc 1 complex can be regulated in response to respiratory conditions.

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

“…In contrast, when carbonate buffer with pH 10.8 was used, Taz1 remained entirely in the pellet fraction, whereas the soluble protein F 1 ␤, of the F 1 F o -ATPase, was completely extracted ( Figure 2C, lane 8 vs. 10). A similar behavior has been reported for other integral membrane proteins, such as the Rieske Fe/S-protein of the bc 1 complex (Hartl et al, 1986;Truscott et al, 2003), which spans the inner membrane with a single transmembrane helix that is in close contact with other integral membrane proteins (Lange and Hunte, 2002). In addition, the inner membrane protein, Pam18 displays similar characteristics in its extractability .…”

Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action

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