Figure Legends:

Figure 1. Composite structure of vertebrate mitochondrial cytochrome c1. The dark horizontal band indicates the probable membrane position. The left and right figures are related by a rotation of 90 about the perpendicular to the membrane. Subunits 1, 2, and 11 are from 1QCR; subunits 3-5 and 8 are from 1BCC; 6, 7, 9, and 10 from 1BE3. The different structures were aligned by superimposing the transmembrane helices of the cytochrome b dimer before selecting subunits for the composite.

Figure 2. Subunit interaction matrix for the bc1 complex structure 1BE3. The letters A-J refer to the chain letters of subunits 1-10 in the monomer in the coordinates file, and N-W to symmetry-mates generated by the crystallographic symmetry operator. The name or number of each subunit is also given in the first column. The principle diagonal is marked with "", and values below the diagonal are omitted to avoid redundancy. A "C" indicates that two subunits have a contact, a "D" indicates a contact between the same subunit in the two monomers. "Contact" was taken to mean approach of two atoms within 4 , center to center. A "clickable" version of this figure is available in the online supplemental materials accessible from the Annual Reviews web site, in which clicking on a "C" or "D" takes the reader to a list of the specific atoms involved in the contact.

Figure 3. Ligation of cytochrome b hemes by histidines in two transmembrane helices. Left- as envisioned based on hydropathy plots, natural sequence variation, inhibitor resistant mutants, and site-directed mutagenesis. Right, as determined by x-ray crystallography. Figure from reference [133a] (left) and from coordinates 1BCC (right).

Figure 4. Secondary structure diagram of cytochrome b from structure 1bcc.

Figure 5. Electron density of heme-containing 4-helix bundle, showing support of the axial-ligand imidazoles by all four helices. The structure is that of 1BCC, and the electron density map is calculated with experimental phases improved by averaging and contoured at 2.0 s (blue) and 12.5 s (orange).

Figure 6. Model of the high-potential electron transfer chain of the bc1 complex. The Rieske ISP and cytochrome c1 are from our beef P6522 crystals. Cytochrome c is positioned to appose the exposed C corner of the cytochromes c and c1. Red and green spheres represent the {Fe2S2] cluster, and gray ball-and-stick models represent the hemes. Figure from Zhang et al [15]

Figure 7. Dimer-like noncrystallographic symmetry observed in two crystal forms of Chlamydomonas cytochrome f. Above is a "top" view, looking down the 2-fold axis of symmetry. Below is a side view, looking parallel to a hypothetical membrane plane constructed perpendicular to the 2-fold. The blue and yellow space-filling models are monomers a and b (from two different asymmetric units) from the structure 1CFM. The hemes are shown as red space-filling models. The magenta backbone drawings are plastocyanin from structure 2PCF, oriented with the operators that best superimpose cytochrome f of that structure on each monomer of the Chlamydomonas dimer. The copper atom of plastocyanin is shown as a green sphere. From reference [216]

Figure 8. Schematic representation of the modified Q-cycle in the context of the structure. The structure of a "functional monomer" of the bc1 complex abstracted from structure 1BCC [15](7) is shown, with the catalytic sites emphasized. The binding of cyt c (red) to cyt c1 (blue) is shown by a model of yeast cyt c positioned at the reaction interface suggested by analysis of co-crystals (Berry et al., unpublished). The Qo- and Qi-sites in cyt b (cyan) are indicated by SQo and SQi for the intermediate semiquinone species thought to function at the sites. The ISP is shown in yellow. Protein is represented by the surfaces of the subunits; prosthetic groups are shown with metals indicated by spacefilling spheres, and heme rings by stick models, labeled as follows: [2Fe-2S]-cluster, Fe2S2; heme c1, c1; heme bL, bL; heme bH, bH. Inhibitors discussed in the text are indicated close to the site at which they function. Electron transfer events are shown by solid blue arrows, proton uptake or release is indicated by thin red arrows; substrate and product binding by open black arrows. The coupling membrane is represented by the gray area.

Figure 9. Scheme showing the mechanism proposed for reactions at the Qo-site after formation of the reaction complex. Numbers indicate the sequence of reactions. In the text, the italic numbers refer to processes numbered in the Figure.

Figure 10. Transmembrane helix prediction for cytochrome b from Mycobacterium, beef, and Chlorobium. Red line: Transmembrane helix preference, Blue line: Beta preference. Green line: Modified hydrophobic moment index (see ref. [302a]). Dark red line (below abscisa): Predicted transmembrane helix position. Calculated by methods in ref 302a using default parameters by the WWW server at URL

Figure 11. Phylogenetic trees based on (A) cytochrome b, (B) the Rieske ISP, and (C) 16S rRNA. Details are described in the text.

Figure 12. Sequence homology between Aquifex and Helicobacter cytochromes and mitochondrial cyt c in the region from helix H3 to H5. The designation of helices and methionine ligand in the top two lines is based on the structure of cyt c. Sequence identifiers are: Cyt. c: Bovine mitochondrial cyt c. Aquif. a.: Cytochrome from Aquifex aeolicus. Helicob #1 and #2: Domains 1 and 2 of the Helicobacter pylori cytochrome