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 Footnotes

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 contains as many as 11 subunits per monomer. The structure shown to the right has 9. (The 'default scene' green link available in the 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. The link to OCA in the green box below contains additional information on the complete complex and the individual peptide components.) of the complex within the inner mitochondrial membrane with labels. reveals that one of the peptides of each subunit invades the space of the other subunit. of each monomeric unit have a direct role in the passage of electrons in the respiratory chain. The subunits that are colored are active in the electron transport chain. The grey peptides have other catalytic activities and functions, and the interior spaces which are created by the positions of the other subunits have a role in the movement of the substrates from one active site to another active site within the complex. 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), head domain which contains the Fe/S center and hinge domain (short segment between the other two).

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 binds at one of the sites, Q_P, and the inhibitor stigmatellin also binds at this site in both cytochrome b's (Stigmatellin is shown in the applet below.^[1])(), and the site is adjacent to the b_L heme. The other site, Q_N, binds ubiquinone, and outlines this site which is 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 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 . Make a mental snap shot of how close the Risieke head and Fe/S center is to cyto b (green) and Q_P site (red spacefill) in order to compare it to the next scene. The is intermediate between the other two positions. This view is generated by 1BGY.pdb and takes longer to load since a new pdb file is loading, and it does not have stigmatellin bound at Q_P (colored teal), therefore the Rieske protein is not as close to cyto b but is in an intermediate position between cyto's b & c1. The is the Cyto c1 position in which the Fe/S contacts the cyto c1 heme through the second His which is hydrogen bonded to a carboxylate oxygen of the heme in c1. 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 1KYO modified Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The cycle starts with the binding of UQH₂, ubiquinol, to cytochrome b at a Q_P site. In the applet to the right the Q_P site is binding stigmatellin. This binding causes the Rieske protein to flex at the hinge region rotating the Fe/S head so that the His which is bound to the Fe/S also binds at Q_P. 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) After Fe is reduced by the UQH ^-, the Rieske head rotates & the Fe/S head 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

Footnotes

1. ↑ The structure shown in the second applet was produced by modifying 1KYO.pdb. The Jmol command 'write file' was used to make a pdb file that contained only the 6 active subunits and cytochrome c (c,d,e,n,o,p,w)and the cofactors of those peptides.