The bc1-complex


The structure shown is from a set of coordinates kindly made available by Dr. Ed Berry, of the bc1-complex from chicken heart mitochondria. The structure is based on diffraction data to 3.0 Å resolution. Click here to view the complete dimeric complex (these coordinate data sets can be obtained by appropriate manipulation of the monomeric structures submitted to the Brookhaven Protein Data Bank). Two of the models below are abstracted from the complete set to show the three catalytic subunits of one monomer, with various prosthetic groups. The other two are the crystallographic monomers of the PDB files. Click here for a summary of the files.
In the initial view, the catalytic subunits of a functional monomer are shown, colored by chain. The protein is shown as a backbone model, and prosthetic groups are wireframe models, colored as follows: hemes bH (top) and bL, magenta; heme c1, red; Fe2S2 center, spacefilling CPK-colored spheres; Qi, yellow; phospholipids and detegent, cyan.
The N-phase (mitochondrial matrix) is at the top, and the P-phase (intermembrane space) at the bottom. d three or four lipids or detergents.

The catalytic subunits - overall view

    Restore wireframe view
  1. Show heme groups of cytochrome b as spacefilling models. Heme bH is red; heme bL is magenta.
  2. Show histine ligands to the hemes as orange spacefilling models.
  3. Show conserved glycines in helices A and C as white spacefilling models.
  4. Show some of the residues which affect the Qo-site when changed by mutagenesis,as ball and stick models in CPK-coloring. Stigmatellin, if present, is shown as an orange stick model
  5. Show some of the residues which affect the Qi-site when changed by mutagenesis, as ball and stick models in CPK-coloring. Qi or antimycin, if present, are shown as yellow stick models.
  6. Richardson cartoon of structure.
  7. Spacefilling model of the catalytic subunits, with prosthetic groups. Cyt b, blue; cyt c1, red; ISP, green; b-hemes, magenta; c-heme, dark red; Qi or antimycin, yellow; stigmatellin, orange; others, cyan

Heme binding domains of cytochrome b

  1. Zoom in on residues involved in ligation of hem bL.
  2. Zoom in on residues involved in ligation of hem bH.

The inhibitor binding sites

The spans contibuting to the Qo-site. Helix C (C-terminal end), blue; cd-helix, blue-green; ef-loop, green; -PEWY- , yellow; ef-helix, orange; helix F (N-terminal end), red. Stigmatellin (or other occupant, if any) (white), and heme bL (magenta) as spacefilling models. Spans shown are those predicted from modelling studies, and sites of inhibitor resistance.
The spans contributing to the Qi-site. Helix a and aA-loop, blue; helix A (N-terminal end), greenblue; helix B (heme ligation), cyan; helix D (C-terminal end), green; de-loop, yellow; helix E (N-terminal end), yellow. Antimycin or Qi (white) and cyt bH (magenta) as spacefilling models. Spans shown are those predicted from modelling studies, and sites of inhibitor resistance.
    The following models show the approximate positions of inhibitors or quinone, and features of the structure associated with the catalytic sites.

    The following buttons will only work if the appropriate model is loaded.

  1. Show the position of the Qo-site occupant (if any) as a spacefilling model.
  2. Show the position of Qi or antimycin as a spacefilling model.
  3. A more detailed look at the Qi-site, with antimycin or quinone in place.
  4. A more detailed look at the Qo-site, with stigmatellin (or myxothiazol, or MOA-stilbene, or Qo) in place.
  5. White background, black labels. Black background, white labels.

Liganding of occupant at the Qo-site

His-161 of ISP and Glu-272 of cyt b, - ligands involved in proton processing, simple view.

Show surface of protein with Qo-site occupant in place, and His-161 of ISP and Glu-272 of cyt b as ligands.

    Note:
  1. The initial script may take up to several minutes (depending on processor and memory capacity) to generate the surface. Be patient!
  2. Only the exterior surface is seen.

Generate surface. View of cyt b with Fe2S2, occupant, and heme bL approximately in the screen plane.
Rotate 45o around y-axis.  Rotate 45o around x-axis.  Rotate 45o around z-axis.
Rotate -45o around y-axis.  Rotate -45o around x-axis.  Rotate -45o around z-axis.
Hint: Rotation, pan, zoom, and slab, work much faster with the surface turned off.
Surface off  Surface on  Surface transparent (toggle)

    Inhibitor resistance mutations.
  1. Residues at the Qi-site at which modification leads to inhibitor resistance.
    Yellow, Diuron and antimycin resistance;
    Orange, Diuron and HQNO resistance;
    Red, HQNO resistance;
    Brown, HQNO and funiculosin resistance;
    Green, funiculosin resistance or sensitivity;
    Cyan, antimycin and funiculosin resistance;
    Blue, antimycin resistance.
    Residues in CPK-coloring are heme ligands (H98, R101, and H197), or a possible ligand to Qi (H202).
  2. Residues at the Qo-site at which modification leads to inhibitor resistance.
    Yellow, myxothiazol resistant sites;
    Red, stigmatellin resistance sites;
    Green, residues at which modification leads to resistance to both inhibitors.
    Stigmatellin is shown as a ball and stick model, colored light blue. The heme of cyt bL is shown as a magenta wireframe model. The iron sulfur protein is shown in the stigmatellin induced configuration, as an orange backbone model.

  3. See Table of data (Brasseur et al., 1996) from which the residues shown in these scripts have been selected.
  4. Residues at which mutation produces a modified gx band. 
    Yellow, normal occupancy but little or no rate; 
    Red, empty, but moderate rate; 
    Orange, different substitutions have either "red" or "yellow" effects; 
    Magenta, empty, and little or no rate; 
    Blue, some mutations are "magenta", and some "green-blue"; 
    Violet, partially occupied, slow rate, hyper sensitive to myxothiazol; 
    Green-blue, normal occupancy, moderate rate. 
    Also shown are residues (Leu-142 (brown) and Gly-143 (grey)) in the ISP at which mutation induced changes in the gx=1.800 signal, and loss of rate. Heme is orange. Stigmatelin is shown as a ball and stick models in cyan.

  5. See Table of data on which this script is based.
  6. Residues in cytochrome b with which mutants at Gly-143 in ISP are expected to make contact. The Ca-atom of Gly-143 is colored white.
  7. Residues in cytochrome b at the interface with the ISP are shown as stick models. Atoms close to the ISP are colored greenblue (within 5.0 Å), green (within 3.5 Å) or yellow (within 2.5 Å). Residues close to this interface at which mutation gives rise to a loss of the gx=1.800 signal are shown as ball and stick models; atoms further away than 5.0 Å are blue. The DCCD-binding group Glu-163 is colored cyan. These residues are numbered at their Ca-atoms. Cytochrome b backbone is blue, ISP backbone is yellow.
  8. For views of the residues on cytochrome b at the interface with ISP, and of the Qo-site, with stigmatellin in place, either load one of the file with ISP in the stigmatellin position (above) or the complete complex
    .

  9. Turn labels off.

Physico-cemical views

    Restore wireframe view
  1. Spacefilling model colored to show residue polarity. Hydrophobic, white; polar, green; basic, blue; acidic, red.
  2. ISP subunit colored to show degree of conservation of redisues. The color-coding is red -> yellow -> green -> greenblue -> blue, for most conserved to least conserved. Note that the cone of residues around the 2Fe2S center is completely conserved; this is the surface which docks in the cyt b interface.
  3. Conservation profile of cyt b subunit. Note that the docking socket on cyt b for the SP is also highly conserved.

Show helices in cytochrome b

    Restore wireframe view
  1. Helix a, white Helix A, yellow Helix ab, green Helix B, blue-green
  2. Helix bc, cyan Helix C, blue Helix cd, violet Helix D, orange
  3. Helix E, orange-red -PEWYF-, white Helix ef, red
  4. Helix F, gray Helix G, magenta Helix H, dark gray
 

H-bonding of some conserved residues

Click on the button to show the residue as a ball and stick model in CPK-coloring, with all atoms within 6.0 Å as wireframes. All N, O and S atoms wihin 3.5 Å are shown as ball and stick models. The backbone chain of the complex is shown in chain color.

Enable distance monitors for screen picking. Click atom 1, then atom 2 to get display of distance between them. (Click on right-hand image for accurate picking). Screen Monitor on.
Disable screen picking Screen Monitor off.

Cytochrome b (Numbering is for avian mitchonrial complex)

 

Leu22 
Pro23 
Trp32 
Asn33 
Gly35 
Leu38 
Cys38 
Gln45 
Gly49 
Gly77 
His84 
Asn86 
Gly87 
Ser89 
Phe91 
His98 
Arg101 
Gly102 
Leu103 
Tyr104 
Tyr105 
Ser107 
Tyr108 
Trp114 
Gly117 
Gly131 
Tyr132 
Gln138 
Met139 
Ser140 
Trp142 
Val146 
Ile147 
Thr148 
Pro155 
Gly158 
Gly168 
Thr175 
Leu176 
His183 
Phe184 
Pro187 
His197 
Leu201 
His202 
Gly205 
Phe221 
Lys228 
Asp229 
Gly252 
Asn256 
Asn261 
Pro262 
Pro271 
Glu272 
Trp273 
Tyr274 
Phe275 
Leu276 
Phe277 
Tyr279 
Ile281 
Leu282 
Arg283 
Pro286 
Lys288 
Gly291 
Val292 
Leu295 
Leu336 
Trp338 
Pro347 
To view other residues, and their physico-chemical context, try out the Chime Protein Viewer with Command Line interface. (Use the PDB 4-char ID, and Remote file access facility, unless you have made a local copy)

Cytochrome c1

  1. Cartoon of cyt c1 showing structure.
  2. The heme binding residues.
  3. Conserved acidic residues on cyt c binding face (?) and dimer interface.
  4. Preliminary conservation profile of cyt c1 subunit (the current assignment of side-chains is based on the bovine sequence, since the chicken sequence is not yet available).
©Copyright 1996, Antony Crofts, University of Illinois at Urbana-Champaign, a-crofts@uiuc.edu