Complex III of Electron Transport Chain: Difference between revisions

Each cytochrome b contains<scene name='Complex_III_of_Electron_Transport_Chain/Hem_cyto_b/5'> two hemes</scene> (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 substrate binding sites. One of these two sites, Q_P, binds [http://en.wikipedia.org/wiki/Ubiquinol ubiquinol] or the inhibitor stigmatellin (<font color='red'>Stigmatellin</font> is shown at this site in the applet below.<ref name=1KYOmodified>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. Since 1KYO.pdb contains stigmatellin bound at the Q_P sites, stigmatellin will be used to represent ubiquinol at Q_P in the modified pdb file.  </ref>), and the site is adjacent to the b_L heme (<scene name='Complex_III_of_Electron_Transport_Chain/Stigmatellin/1' target='second'>Reset initial scene </scene>). The other site, Q_N, is located adjacent to the b_H heme and binds [[Coenzyme_Q10|ubiquinone]], and since it is empty in the PDB file, it is shown as <scene name='Complex_III_of_Electron_Transport_Chain/Surface_antimycin/1' target='second'>a surface with pockets</scene>.  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.<br>

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<scene name='Complex_III_of_Electron_Transport_Chain/Fes/4'>Fe/S center</scene> is in the head  of each <font color='red'>Rieske protein</font>. Each of the Fe/S centers is complexed with <scene name='Complex_III_of_Electron_Transport_Chain/Fes_2_his/1'>two His</scene>. As a result of bending at the <scene name='Complex_III_of_Electron_Transport_Chain/Fes_hinge/4'>hinge region</scene> (colored cyan) the head can be in one of three possible positions.  Here the Fe/S head is in the '<scene name='Complex_III_of_Electron_Transport_Chain/Posit_cytob_closeup/2'>cyto b position</scene>' in which a His of the Fe/S/His complex is in contact with the ubiquinol (actually <font color='red'>stigmatellin</font> in this model) bound at the Q_P site of cyto b. Wider view of '<scene name='Complex_III_of_Electron_Transport_Chain/Posit_cyto_b/2'>cyto b position</scene>'. Notice that the His of the <font color='red'>Risieke head</font> is in contact with <font color='red'>stigmatellin</font> in the Q_P site and the stigmatellin is positioned on a straight line between the two hemes in the cyto c1 subunits. The '<scene name='Complex_III_of_Electron_Transport_Chain/Posit_intermed_1bgy/2'>Int position</scene>' is shown with a PDB file <ref>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</ref><ref name=1BGYmodified>The pdb file used for this scene and those of the next couple were generated by a modification of 1BGY.pdb. It contains data for only the six active subunits (chains c, d, e, o, p, q) and their cofactors.  The pdb file contains no substrates or inhibitors bound at Q_P or Q_N so the computed surface of these interior spaces is one large surface which outlines all four binding sites.</ref>  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 '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, <scene name='Complex_III_of_Electron_Transport_Chain/Posit_c1_1bgy/1'>here</scene> 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'.

<applet load='1bgy_modified.pdb' size='400' frame='true' align='right' scene ='Complex_III_of_Electron_Transport_Chain/Posit_intermed_1bgy_arrowless/1'  /> At the start of the cycle the Q_P site of cytochrome b is empty and the Fe/S center of the Rieske protein is in the 'Int position'. (<scene name='Complex_III_of_Electron_Transport_Chain/Posit_intermed_1bgy_arrowless/1'>Reset initial scene.</scene>) With the binding of <scene name='Complex_III_of_Electron_Transport_Chain/Posit_intermed_1bgy_cycle/2'>ubiquinol</scene>, UQH₂, to the Q_P 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 <scene name='Complex_III_of_Electron_Transport_Chain/Posit_cyto_b_cycle/1'>ubiquinol</scene> (<font color=red>stigmatellin</font> in this model)<ref name=1KYOmodified/>.  Binding of the His to UQH₂ reduces its pK, and the UQH₂ loses a proton to become [http://en.wikipedia.org/wiki/Ubiquinol UQH^{<big> -</big>}].  The position of Q_P in the complex is such that the proton which is lost <scene name='Complex_III_of_Electron_Transport_Chain/Posit_cyto_b_cycle_arrow/1'>diffuses to the intermembrane space</scene>. 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^{<big> -</big>} becomes UQH<big>^•</big>, a [http://en.wikipedia.org/wiki/Ubiquinol semiquinone], which loses a proton and becomes UQ^{<big> • -</big>}, 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^{<big> -</big>}, the Rieske head rotates & the Fe/S moves to cytochrome c1, <scene name='Complex_III_of_Electron_Transport_Chain/Posit_cyto_b_cycle_move_c1/1'>the "c1" position</scene>, 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 <scene name='Complex_III_of_Electron_Transport_Chain/Cyto_c_2_cycle/1'>cytochrome c binds</scene> 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 second half of the Q cycle starts the same as the first half with the binding of UQH₂ at the Q_p proceeding from there, it is the same as in the first half and is only different from the first half at the end of the cycle at the Q_n site at which a semi-ubiquinone is reduced to UQH₂ so that during a complete cycle at the Q_n site an UQ is reduced to UQH₂.