Dataset Information

Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels.

ABSTRACT: The respiratory chain or oxidative phosphorylation system (OxPhos) generates most of the chemical energy (ATP) used by our cells. The cytochrome c oxidase (CcO) is one of three protein complexes of OxPhos building up a proton gradient across the inner mitochondrial membrane, which is ultimately used by the ATP synthase to produce ATP. We present molecular dynamic simulations of CcO in a mimic of the mitochondrial membrane, and identify precise binding sites of cardiolipin (CL, signature phospholipid of mitochondria) on the protein surface. Two of these CL binding sites reveal pathways linking CLs to the entrance of the D and H proton channels across CcO. CLs being able to carry protons our results strongly support an involvement of CLs in the proton delivery machinery to CcO. The ubiquitous nature of CL interactions with the components of the OxPhos suggests that this delivery mechanism might extend to the other respiratory complexes.

SUBMITTER: Arnarez C

PROVIDER: S-EPMC3570132 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels.

Arnarez C C Marrink S J SJ Periole X X

Scientific reports 20130212

The respiratory chain or oxidative phosphorylation system (OxPhos) generates most of the chemical energy (ATP) used by our cells. The cytochrome c oxidase (CcO) is one of three protein complexes of OxPhos building up a proton gradient across the inner mitochondrial membrane, which is ultimately used by the ATP synthase to produce ATP. We present molecular dynamic simulations of CcO in a mimic of the mitochondrial membrane, and identify precise binding sites of cardiolipin (CL, signature phosphol ...[more]

PMID: 23405277

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Project description:Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to water. The ("chemical") protons required for this reaction and those pumped are taken up via two distinct channels, named D-channel and K-channel, in a step-wise and highly regulated fashion. In the reductive phase of the catalytic cycle, both channels transport protons so that the pumped proton passes the D-channel before the "chemical" proton has crossed the K-channel. By performing molecular dynamics simulations of CcO in the O→E redox state (after the arrival of the first reducing electron) with various combinations of protonation states of the D- and K-channels, we analysed the effect of protonation on the two channels. In agreement with previous work, the amount of water observed in the D-channel was significantly higher when the terminal residue E286 was not (yet) protonated than when the proton arrived at this end of the D-channel and E286 was neutral. Since a sufficient number of water molecules in the channel is necessary for proton transport, this can be understood as E286 facilitating its own protonation. K-channel hydration shows an even higher dependence on the location of the excess proton in the K-channel. Also in agreement with previous work, the K-channel exhibits a very low hydration level that likely hinders proton transfer when the excess proton is located in the lower part of the K-channel, that is, on the N-side of S365. Once the proton has passed S365 (towards the reaction site, the bi-nuclear centre (BNC)), the amount of water in the K-channel provides hydrogen-bond connectivity that renders proton transfer up to Y288 at the BNC feasible. No significant direct effect of the protonation state of one channel on the hydration level, hydrogen-bond connectivity, or interactions between protein residues in the other channel could be observed, rendering proton conductivity in the two channels independent of each other. Regulation of the order of proton uptake and proton passage in the two channels such that the "chemical" proton leaves its channel last must, therefore, be achieved by other means of communication, such as the location of the reducing electron.

Dataset Information

Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels.

Publications

Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels.

Similar Datasets

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