Complex III of Electron Transport Chain
Be aware that the structure in the first scene is large and significant time is required for loading the structure! The other applets load much faster. ContentsIntroductionComplex III of the electron transport chain has a dimeric structure with each monomer containing as many as 11 subunits, but the structure shown to the right has 9. [1] [2]
Coloring one monomeric unit grey reveals this dimeric structure. Notice that one of the peptides of each subunit invades the space of the other monomeric unit, and labels show the orientation of the complex within the inner mitochondrial membrane. Three of the subunits (colored green, blue and red) of each monomeric unit have a direct role in the passage of electrons in the respiratory chain. The grey peptides are not assigned a function in the current mechanism of redox reactions of Complex III, but they do have other catalytic activities and functions. For the most part, the two subunits of cytochrome b (colored green) are buried in the complex and have minimal exposure to the intermembrane space and matrix. Cytochrome c1 subunits are positioned on top of cytochrome b and their outer surfaces are exposed to the intermembrane space. They are held in place by helical tails that extend deep into the complex and the membrane. The Rieske subunits are Fe/S proteins with three domains: membrane domain - long helical segment that extends into the membrane, hinge domain - short segment between the membrane and head domains, and head domain - contains the Fe/S center and occupies space in the other monomeric unit. Therefore, as will be shown below, the Fe/S center interacts chemically with the cytochrome subunits which are located in the partner monomeric unit. Structure of three active componentsEach cytochrome b contains two hemes (displayed as spacefill and colored cpk). Identify each of the hemes by toggling off the spin and hovering the curser over an atom of the heme. Hem 501 and Hem 502 are in one cytochrome b, and Hem 521 and Hem 522 are in the other one. The two hemes in each cytochrome b are in different environments and therefore have different properties, e.g. reduction potential. Hemes 501 & 521 have a lower potential than the other two and are called bL for low potential, and the other two are called bH for high potential. Each of the cytochrome b's have two substrate binding sites, QP and QN. QP is adjacent to the bL heme and binds ubiquinol[3] or, as in this case, the inhibitor stigmatellin[4]. The other site, QN, is located adjacent to the bH heme and binds ubiquinone, and since it is empty in the PDB file, it is shown as a surface with pockets. In this view you are looking into the lit pocket in which the ubiquinone binds. You can rotate the structure and observe the ubiquinone binding pocket in the other subunit. Each cytochrome c1 contains a heme. Viewing cyto c1 in spacefill as it would be seen from the intermembrane space, there is an opening in the center of the dimeric c1 through which one can see the gray hemes of the cyto b's. Also seen is the gray heme embedded in each of the cyto c1's showing that the heme is located in a crevice which has an opening to the intermembrane space and an opening on the side next to the Rieske protein (heme oxygens are seen). The opening seen in this view permits the cyto c1 heme to make contact with the Rieske protein, and the one on the surface of cyto c1 permits contact with cytochrome c when it binds to cytochrome c1 at the intermembrane surface. There are negatively charged acidic residues which attract the complementary positive charges on cytochrome c, a basic protein. Cytochrome c (colored cyan) bound to one cyto c1 as viewed from intermembrane space and from slice through membrane showing that the hemes of the two cytochromes are in close contact. The two hemes seen through transparent spacefill. Fe/S center is in the head of each Rieske protein. Each of the Fe/S centers is complexed with two His. As a result of bending at the hinge region (colored cyan) the head can be in one of three possible positions. Here the Fe/S head is in the 'cyto b position' in which a His of the Fe/S/His complex is in contact with the ubiquinol (actually stigmatellin in this model) bound at the QP site of cyto b. Wider view of 'cyto b position'. Notice that the His of the Rieske head is in contact with stigmatellin in the QP site and the stigmatellin is positioned on a straight line between the two hemes in the cyto c1 subunits. The 'Int position' is shown with a PDB file [5][6] that does not have stigmatellin bound at QP, and the black arrow is pointing to the QP pocket. This pocket is on a straight line between the hemes of cyto c1, as the QP site was positioned in the previous view of the 'cyto b position', but the Fe/S center is not in contact with the QP binding pocket and is in a position intermediate between the cyto b and cyto c1 positions. In the 'Cyto c1 position', the third position, the second His of the Fe/S is in contact with the cyto c1 heme through a hydrogen bond to a carboxylate oxygen of the heme, but since it can not be shown directly, here a black arrow indicates the direction of movement from 'Int position' to the 'Cyto c1' position, and an orange arrow indicates the direction of movement from the 'Int position' to the 'Cyto b position'. Q CycleAt the start of the cycle the QP site of cytochrome b is empty and the Fe/S center of the Rieske protein is in the 'Int position'. (Reset initial scene.) With the binding of ubiquinol, UQH2, to the QP site (black arrow) of cytochrome b the Rieske protein moves to the 'cyto b position' by flexing at the hinge region and rotating the Fe/S head so that the His which is bound to the Fe/S also binds to ubiquinol (stigmatellin in this model)[4]. Binding of the His to UQH2 reduces its pK, and the UQH2 loses a proton to become UQH -[7]. The position of QP in the complex is such that the proton which is lost diffuses to the intermembrane space. After UQH2 loses the proton and becomes UQH -, it passes an electron through the His to the Fe+3 reducing it to Fe+2. With the loss of the electron the UQH - becomes UQH •, a semiquinone[8], which loses a proton and becomes UQ • -, the conjugate base of the semiquinone. The proton diffuses to the intermembrane space, as the first one did. (The fate of the semiquinone can be traced starting with the next paragraph.) After Fe in the Fe/S center is reduced by the UQH -, the Rieske head rotates & the Fe/S moves to cytochrome c1, the "c1" position, so that the second His bound to Fe/S binds to the heme of cytochrome c1. When the His contacts the heme of cytochrome c1 an electron is rapidly passed from the Fe/S through the His to the Fe of the cytochrome c1 heme, and since it is now in the oxidized form, the Rieske protein returns to the "Int" position. The cytochrome c1 heme is now reduced, and when cytochrome c binds to it the electron is passed from the c1 heme to the c heme (black arrow). The cytochrome c then releases from the membrane and diffuses through the intermembrane space to Complex IV. Returning to UQ • -, the conjugate base of the semiquinone[9], which was formed at Qp as described above and is shown here as stigmatellin, the UQ • - is oxidized to the full UQ when it passes an electron to heme bL. The electron is then passed from the Fe of heme bL to the Fe of Heme bH, and with Heme bH being next to UQ bound at the Qn site (Binding site is located on the surface with a black arrow.), the electron is passed to UQ. With only one electron being passed in this series of reaction, the UQ is reduced to UQ • -, and when it accepts a proton which comes from the matrix it becomes UQH •. The end products of the first half of the Q cycle are UQ at the Qp site, reduced cyt c and semi-ubiquinone at the Qn site. The second half of the Q cycle starts the same as the first half with the binding of UQH2 at the Qp, and proceeding from there, it is the same as in the first half except that in the second half at the end of the cycle at the Qn site the semi-ubiquinone is reduced to UQH2 so that during a complete cycle at the Qn site UQ is reduced to UQH2. SUMMARY OF Q CYCLE REACTIONS: 2 ubiquinols oxidized to 2 ubiquinones View Interior of Qp and Qn SitesThe scene on the right shows the surface of interior cavities of Complex III with the four substrate binding sites labeled.[6] (Reset initial scene.) The PDB file used to generate the display has no cofactors binding at these sites so they are empty. After turning on the Slicer observe that, as the surface rotates, its interior is exposed and that the empty binding sites are joined by connecting interior channels. These channels permit the UQ that is formed in Qp to diffuse to Qn where it is reduced to UQH2, and in turn the UQH2 can diffuse to a Qp where it is oxidized to UQ.
3D structures of complex III of electron transport chain
| ||||||||||||
Notes and References
Proteopedia Page Contributors and Editors (what is this?)
Karl Oberholser, Michal Harel, Jaime Prilusky, Eran Hodis, Alexander Berchansky
