Interplay of Hydration and Protonation Dynamics in the K-Channel of Cytochrome c Oxidase

Biomolecules. 2022 Nov 1;12(11):1615. doi: 10.3390/biom12111615.

Abstract

Cytochrome c oxidase is a membrane protein of the respiratory chain that consumes protons and molecular oxygen to produce water and uses the resulting energy to pump protons across the membrane. Our molecular dynamics simulations with an excess proton located at different positions in one of the proton-conducting channels, the K-channel, show a clear dependence of the number of water molecules inside the channel on the proton position. A higher hydration level facilitates the formation of hydrogen-bonded chains along which proton transfer can occur. However, a sufficiently high hydration level for such proton transport is observed only when the excess proton is located above S365, i.e., the lower third of the channel. From the channel entrance up to this point, proton transport is via water molecules as proton carriers. These hydronium ions move with their surrounding water molecules, up to K362, filling and widening the channel. The conformation of K362 depends on its own protonation state and on the hydration level, suggesting its role to be proton transport from a hydronium ion at the height of K362 to the upper part of the channel via a conformational change. The protonation-dependent conformational dynamics of E101 at the bottom of the channel renders proton transfer via E101 unlikely. Instead, its role is rather that of an amplifier of H96's proton affinity, suggesting H96 as the initial proton acceptor.

Keywords: cytochrome c oxidase; hydration level; molecular dynamics simulations; proton transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Transport
  • Electron Transport Complex IV* / metabolism
  • Molecular Dynamics Simulation
  • Protons*
  • Water / metabolism

Substances

  • Electron Transport Complex IV
  • Protons
  • Water

Grants and funding

This research was funded by Deutsche Forschungsgemeinschaft (DFG) through project C5 of the CRC1078 “Protonation dynamics in protein function”. The APC was funded by Freie Universität Berlin.