A1 Refereed original research article in a scientific journal
Key role of water in proton transfer at the Q(o)-site of the cytochrome bc(1) complex predicted by atomistic molecular dynamics simulations
Authors: Postila PA, Kaszuba K, Sarewicz M, Osyczka A, Vattulainen I, Rog T
Publisher: ELSEVIER SCIENCE BV
Publication year: 2013
Journal: BBA - Bioenergetics
Journal name in source: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Journal acronym: BBA-BIOENERGETICS
Volume: 1827
First page : 761
Last page: 768
Number of pages: 8
ISSN: 0005-2728
DOI: https://doi.org/10.1016/j.bbabio.2013.02.005
Abstract
Cytochrome (cyt) bc(1) complex, which is an integral part of the respiratory chain and related energy-conserving systems, has two quinone-binding cavities (Q(o)- and Q(i)-sites), where the substrate participates in electron and proton transfer. Due to its complexity, many of the mechanistic details of the cyt bc(1) function have remained unclear especially regarding the substrate binding at the Q(o)-site. In this work we address this issue by performing extensive atomistic molecular dynamics simulations with the cyt bc(1) complex of Rhodobacter capsulatus embedded in a lipid bilayer. Based on the simulations we are able to show the atom-level binding modes of two substrate forms: quinol (QH(2)) and quinone (Q). The QH(2) binding at the Q(o)-site involves a coordinated water arrangement that produces an exceptionally close and stable interaction between the cyt b and iron sulfur protein subunits. In this arrangement water molecules are positioned suitably in relation to the hydroxyls of the QH(2) ring to act as the primary acceptors of protons detaching from the oxidized substrate. In contrast, water does not have a similar role in the Q binding at the Q(o)-site. Moreover, the coordinated water molecule is also a prime candidate to act as a structural element, gating for short-circuit suppression at the Q(o)-site. (c) 2013 Elsevier B.V. All rights reserved.
Cytochrome (cyt) bc(1) complex, which is an integral part of the respiratory chain and related energy-conserving systems, has two quinone-binding cavities (Q(o)- and Q(i)-sites), where the substrate participates in electron and proton transfer. Due to its complexity, many of the mechanistic details of the cyt bc(1) function have remained unclear especially regarding the substrate binding at the Q(o)-site. In this work we address this issue by performing extensive atomistic molecular dynamics simulations with the cyt bc(1) complex of Rhodobacter capsulatus embedded in a lipid bilayer. Based on the simulations we are able to show the atom-level binding modes of two substrate forms: quinol (QH(2)) and quinone (Q). The QH(2) binding at the Q(o)-site involves a coordinated water arrangement that produces an exceptionally close and stable interaction between the cyt b and iron sulfur protein subunits. In this arrangement water molecules are positioned suitably in relation to the hydroxyls of the QH(2) ring to act as the primary acceptors of protons detaching from the oxidized substrate. In contrast, water does not have a similar role in the Q binding at the Q(o)-site. Moreover, the coordinated water molecule is also a prime candidate to act as a structural element, gating for short-circuit suppression at the Q(o)-site. (c) 2013 Elsevier B.V. All rights reserved.
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