Complex III of Electron Transport Chain

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UNDER CONSTRUCTION
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Contents 1 Introduction 2 Structure of three active components 3 Q Cycle 4 View Interior of Q Binding Sites 5 Notes and References

Introduction

spinqualitylabelsall models PDB ID 1kyo Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1kyo, resolution 2.97Å ()
Ligands:	, ,
Non-Standard Residues:
Activity:	Ubiquinol--cytochrome-c reductase, with EC number 1.10.2.2
Related:	1ezv, 1kb9
Structural annotation: Resources: CATH : 1Kyoa02, 1Kyoa01, 1Kyob02, 1Kyob01, 1Kyoc00, 1Kyod01, 1Kyod02, 1Kyoe01, 1Kyoe02, 1Kyof00, 1Kyog00, 1Kyoh00, 1Kyoi00, 1Kyoj00, 1Kyok00, 1Kyol02, 1Kyol01, 1Kyom02, 1Kyom01, 1Kyon00, 1Kyoo01, 1Kyoo02, 1Kyop01, 1Kyop02, 1Kyoq00, 1Kyor00, 1Kyos00, 1Kyot00, 1Kyou00, 1Kyov00, 1Kyow00 InterPro : Ipr011237, Ipr001431, Ipr007863, Ipr011249, Ipr011765, Ipr005798, Ipr005797, Ipr002326, Ipr009056, Ipr004192, Ipr006317, Ipr005806, Ipr014349, Ipr005805, Ipr003422, Ipr003197, Ipr004205, Ipr008027, Ipr003088, Ipr012125, Ipr002327 Pfam : PF00675, PF05193, PF00032, PF00033, PF02167, PF02921, PF00355, PF02271, PF02939, PF05365, PF00034 SCOP : d1kyoa2, d1kyoa1, d1kyob2, d1kyob1, d1kyoc2, d1kyoc3, d1kyod2, d1kyod1, d1kyoe2, d1kyoe1, d1kyof_, d1kyog_, d1kyoh_, d1kyoi_, d1kyol1, d1kyol2, d1kyom2, d1kyom1, d1kyon2, d1kyon3, d1kyoo2, d1kyoo1, d1kyop1, d1kyop2, d1kyoq_, d1kyor_, d1kyos_, d1kyot_, d1kyow_ UniProt : P07256, P07257, P00163, P07143, P08067, P00127, P00128, P08525, P22289, P00044
Functional annotation: Cellular component: mitochondrial respiratory chain mitochondrion membrane mitochondrial respiratory chain complex III integral to membrane mitochondrial inner membrane mitochondrial envelope mitochondrial intermembrane space Biological process: aerobic respiration electron transport proteolysis transport mitochondrial electron transport, ubiquinol to cytochrome c oxidative phosphorylation cytochrome bc(1) complex assembly iron-sulfur cluster assembly Molecular function: zinc ion binding protein binding metalloendopeptidase activity ubiquinol-cytochrome-c reductase activity iron ion binding metal ion binding electron transporter, transferring electrons within CoQH2-cytochrome c reductase complex activity oxidoreductase activity heme binding electron carrier activity iron-sulfur cluster binding 2 iron, 2 sulfur cluster binding
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Complex 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]} () reveals this dimeric structure. Notice that one of the peptides of each subunit invades the space of the other monomeric unit. Labels show the orientation of the complex within the inner mitochondrial membrane. of each monomeric unit have a direct role in the passage of electrons in the respiratory chain. The subunits that are colored green, blue and red are active in the electron transport chain. The grey peptides are not assigned a function in the mechanism of Complex III action, but they do have other catalytic activities and functions. The two subunits of cytochrome b (colored green) for the most part 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 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 chemically interacts with cytochrome subunits which are located in the partner monomeric unit.

Structure of three active components

Each cytochrome b contains (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 b_L for low potential, and the other two are called b_H for high potential. Each of the cytochrome b's have two binding sites for substrate. Ubiquinol and the inhibitor stigmatellin bind at one of these sites, Q_P, (Stigmatellin is shown in the applet below.^[3]), and the site is adjacent to the b_L heme (). The other site, Q_N, binds ubiquinone, and since it is empty in the PDB file, it is outlined by which is located adjacent to the b_H heme. 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.

spinqualitylabelsall models PDB ID 1kyo_modified.pdb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Each cytochrome c1 contains . Viewing 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 in this view is the gray heme embedded in each of the cyto c1's showing that the heme is located in a crevice which is open to the intermembrane space and on the (heme oxygens are seen). These openings of the crevice permits the cyto c1 heme to make contact with the Rieske protein and with cytochrome c when it binds to the . There are which attrack the complementary positive charges on cytochrome c, a basic protein. (colored cyan) bound to one cyto c1 as viewed from intermembrane space and from slice through membrane of the two cytochromes are in close contact. The seen through transparent spacefill.

is in the head of each Rieske protein. Each of the Fe/S centers is complexed with . As a result of bending at the (colored cyan) the head can be in one of three possible positions. Here the Fe/S head is in the in which a His of the Fe/S/His complex is in contact with the ubiquinol (actually stigmatellin in this model) bound at the Q_P site of cyto b. Wider view of . Notice that the His of the Risieke head is in contact with stigmatellin in the Q_P site and the stigmatellin is positioned on a straight line between the two hemes in the cyto c1 subunits. The is shown with a PDB file ^[4][5] that does not have stigmatellin bound at Q_P, and the black arrow is pointing to the Q_P pocket. This pocket is on a straight line between the hemes of cyto c1, as the Q_P site was positioned in the previous view of the cyto b position, but the Fe/S center is not in contact with the Q_P binding pocket and is in a position intermediate between the cyto b and cyto c1 positions. In the , 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. Black arrow indicates the direction of movement from Int position to the Cyto c1 position, and the orange arrow indicates the direction of movement from the Int position to the Cyto b position.

Q Cycle

spinqualitylabelsall models PDB ID 1bgy_modified.pdb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

At the start of the cycle the Q_P site is empty and the Fe/S center of the Rieske protein is in the Int position. () With the binding of , UQH₂, to cytochrome b (black arrow) the Rieske protein flexes at the hinge region rotating the Fe/S head so that the His which is bound to the Fe/S also at Q_P (stigmatellin in this model). Binding of the His to UQH₂ reduces its pK, and the UQH₂ loses a proton to become UQH ^-. The position of Q_P in the complex is such that the proton which is lost . 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, 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, , 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 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.

The UQ ^{• -}, the of the semiquinone, which was formed at Qp as described above and is shown here as stigmatellin is oxidized to the full UQ when it to heme b_L. The is then passed from the Fe of heme b_L to the Fe of Heme b_H, and with Heme b_H being next to UQ bound at the Q_n site (Binding site is shown as a .), the is passed to UQ. With only one electron being passed in this series of reaction the UQ is reduced to UQ ^{• -}, and becomes UQH ^• when it accepts a which comes from the matrix. The end products of the first half of the Q cycle are an ubiquinol oxidized to ubiquinone at the Q_p site, a reduced cyt c and an ubiquinone reduced to semi-ubiquinone at the Q_n site.

The second half of the Q cycle is different form the first half in that at the Q_n site at the end of the cycle a semi-ubiquinone is reduced to ubiquinol so that during a complete cycle at the Q_n site an ubiquinone is reduced to ubiquinol.

SUMMARY:
2 ubiquinols oxidized at the Q_p
2 cytochrome c's reduced
1 ubiquinone reduced to ubiquinol
4 hydrogen ions moved from matrix to intermenbrane space

View Interior of Q Binding Sites

spinqualitylabelsall models PDB ID 1bgy_modified.pdb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The applet on the right shows the interior cavities of Complex III with the four Q sites labeled. () 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 is rotated its interior is exposed and that there are interior chambers connecting the different binding sites.

Notes and References

1. ↑ C.Lange,C.Hunte, Crystal Structure of The Yeast Cytochrome BC1 Complex with Its Bound Substrate Cytochrome C., Proc. Natl. Acad. Sci. USA, 99, 2800, 2002
2. ↑ 1KYO.pdb is being used to generate the images in the first applet. The 'default scene' green link available in the first Jmol applet shows the dimer structure along with Heavy Chain (Vh) of Fv-Fragment, Light Chain (Vl) of Fv-Fragment and Cytochrome C, Iso-1 all of which are a part of 1KYO.PDB. Follow the link to OCA in the green table below the applet for additional information on the complete complex and the peptide components.
3. ↑ Since 1KYO.pdb contains stigmatellin bound at the Q_P sites, stigmatellin will be used to represent ubiquinol. This structure and the next several are generated by a modification of 1KYO.pdb. The Jmol command 'write file' was used to make a PDB file that contains only the 6 active subunits and cytochrome c (chains c,d,e,n,o,p,w) and the cofactors of those peptides.
4. ↑ S.Iwata, J.W.Lee,K.Okada,J.K.Lee, M.Iwata, B.Rasmussen, T.A.Link, S.Ramaswamy, B.K.Jap, SCIENCE, 281, 64, 1998
5. ↑ 1BGY.pdb was modified to contain only the six active subunits (chains c, d, e, o, p, q) and their cofactors. 1BGY.pdb contains no cofactors bound at Q_P or Q_N so these binding sites are shown as one large open surface which outlines all four binding sites as pockets.