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Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase

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Abstract

Proton transfer in cytochrome c oxidase (CcO) from the cellular inside to the binuclear redox centre as well as proton pumping through the membrane takes place through proton entrance via two distinct pathways, the D- and K-channel. Both channels show a dependence of their hydration level on the protonation states of their key residues, K362 for the K-channel, and E286 or D132 for the D-channel. In the oxidative half of CcO’s catalytic cycle the D-channel is the proton-conducting path. For this channel, an interplay of protonation state of the D-channel residues with the water and hydrogen-bond dynamics has been observed in molecular dynamics simulations of the CcO protein, embedded in a lipid bi-layer, modelled in different protonation states. Protonation of residue E286 at the end of the D-channel results in a hydrogen-bonded network pointing from E286 to N139, that is against proton transport, and favouring N139 conformations which correspond to a closed asparagine gate (formed by residues N121 and N139). Consequently, the hydration level is lower than with unprotonated E286. In those models, the Asn gate is predominantly open, allowing water molecules to pass and thus increase the hydration level. The hydrogen-bonded network in these states exhibits longer life times of the Asn residues with water than other models and shows the D-channel to be traversable from the entrance, D132, to exit, E286. The D-channel can thus be regarded as auto-regulated with respect to proton transport, allowing proton passage only when required, that is the proton is located at the lower part of the D-channel (D132 to Asn gate) and not at the exit (E286).

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Acknowledgements

We are grateful for computational resources provided by the North-German Supercomputing Alliance (HLRN). IT support by Jens Dreger of the Physics department at Freie Universität Berlin is gratefully acknowledged.

Funding

This study was funded by the Deutsche Forschungsgemeinschaft (DFG) provided through project C5 “Redox-state dependent communication and protonation dynamics in cytochrome c oxidase” in the Sonderforschungsbereich 1078 (SFB 1078) on ’Protonation Dynamics in Protein Function’.

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  1. Ferand Dalatieh

    Present address: R Institute GmbH, Dortustraße 48, 14467, Potsdam, Germany

  2. Tahereh Ghaney and Rene F. Gorriz have contributed equally.

Authors and Affiliations

  1. Institute of Theoretical Physics, Freie Universität Berlin, Arnimallee 14, 14195, Berlin, Germany

    Tahereh Ghane, Rene F. Gorriz, Sandro Wrzalek, Senta Volkenandt, Ferand Dalatieh, Marco Reidelbach & Petra Imhof

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  1. Tahereh Ghane
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Correspondence to Petra Imhof.

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Ghane, T., Gorriz, R.F., Wrzalek, S. et al. Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase. J Membrane Biol 251, 299–314 (2018). https://doi.org/10.1007/s00232-018-0019-x

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