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

Vivek Sharma, Pauliina Ala-Vannesluoma, Ilpo Vattulainen, Mårten Wikström, Tomasz Róg

    Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

    25 Sitaatiot (Scopus)

    Abstrakti

    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.

    AlkuperäiskieliEnglanti
    Sivut690-697
    Sivumäärä8
    JulkaisuBiochimica et Biophysica Acta: Bioenergetics
    Vuosikerta1847
    Numero8
    DOI - pysyväislinkit
    TilaJulkaistu - 17 huhtik. 2015
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

    Julkaisufoorumi-taso

    • Jufo-taso 1

    !!ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology

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