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Role of subunit III and its lipids in the molecular mechanism of cytochrome c oxidase

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Details

Original languageEnglish
Pages (from-to)690-697
Number of pages8
JournalBiochimica et Biophysica Acta: Bioenergetics
Volume1847
Issue number8
DOIs
Publication statusPublished - 17 Apr 2015
Publication typeA1 Journal article-refereed

Abstract

The terminal respiratory enzyme cytochrome c oxidase (CcO) reduces molecular oxygen to water, and pumps protons across the inner mitochondrial membrane, or the plasma membrane of bacteria. A two-subunit CcO harbors all the elements necessary for oxygen reduction and proton pumping. However, it rapidly undergoes turnover-induced irreversible damage, which is effectively prevented by the presence of subunit III and its tightly bound lipids. We have performed classical atomistic molecular dynamics (MD) simulations on a three-subunit CcO, which show the formation of water wires between the polar head groups of lipid molecules bound to subunit III and the proton uptake site Asp91 (Bos taurus enzyme numbering). Continuum electrostatic calculations suggest that these lipids directly influence the proton affinity of Asp91 by 1-2 pK units. We surmise that lipids bound to subunit III influence the rate of proton uptake through the D-pathway, and therefore play a key role in preventing turnover-induced inactivation. Atomistic MD simulations show that subunit III is rapidly hydrated in the absence of internally bound lipids, which is likely to affect the rate of O<inf>2</inf> diffusion into the active-site. The role of subunit III with its indigenous lipids in the molecular mechanism of CcO is discussed.

ASJC Scopus subject areas

Keywords

  • Cardiolipin, Continuum electrostatic, Molecular dynamics simulation, Oxygen diffusion, Water molecule

Publication forum classification

Field of science, Statistics Finland