Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.
Computer Chemistry Center, Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Nägelsbachstrasse 25, 91052 Erlangen, Germany.
Biomolecules. 2022 Nov 1;12(11):1615. doi: 10.3390/biom12111615.
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.
细胞色素 c 氧化酶是一种位于呼吸链中的膜蛋白，它消耗质子和分子氧来产生水，并利用产生的能量将质子泵过膜。我们在一个质子传导通道（K 通道）中的不同位置放置多余质子的分子动力学模拟表明，通道内水分子的数量明显依赖于质子位置。更高的水合水平有助于形成氢键链，质子可以沿着这些链转移。然而，只有当多余的质子位于 S365 上方，即通道的下三分之一处时，才能观察到这种质子传输所需的足够高的水合水平。从通道入口到这一点，质子通过水分子作为质子载体进行传输。这些氢离子与周围的水分子一起移动，直到 K362，填满并拓宽通道。K362 的构象取决于其自身的质子化状态和水合水平，表明其作用是通过构象变化将质子从 K362 高度的氢离子传输到通道的上半部分。通道底部 E101 的质子依赖性构象动力学使得质子通过 E101 转移不太可能。相反，它的作用更像是 H96 质子亲和力的放大器，表明 H96 是初始质子受体。
