dc.contributor.author
Gorriz, Rene F.
dc.contributor.author
Volkenandt, Senta
dc.contributor.author
Imhof, Petra
dc.date.accessioned
2023-08-18T13:10:48Z
dc.date.available
2023-08-18T13:10:48Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40531
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40251
dc.description.abstract
Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to water. The (“chemical”) protons required for this reaction and those pumped are taken up via two distinct channels, named D-channel and K-channel, in a step-wise and highly regulated fashion. In the reductive phase of the catalytic cycle, both channels transport protons so that the pumped proton passes the D-channel before the “chemical” proton has crossed the K-channel. By performing molecular dynamics simulations of CcO in the O→E redox state (after the arrival of the first reducing electron) with various combinations of protonation states of the D- and K-channels, we analysed the effect of protonation on the two channels. In agreement with previous work, the amount of water observed in the D-channel was significantly higher when the terminal residue E286 was not (yet) protonated than when the proton arrived at this end of the D-channel and E286 was neutral. Since a sufficient number of water molecules in the channel is necessary for proton transport, this can be understood as E286 facilitating its own protonation. K-channel hydration shows an even higher dependence on the location of the excess proton in the K-channel. Also in agreement with previous work, the K-channel exhibits a very low hydration level that likely hinders proton transfer when the excess proton is located in the lower part of the K-channel, that is, on the N-side of S365. Once the proton has passed S365 (towards the reaction site, the bi-nuclear centre (BNC)), the amount of water in the K-channel provides hydrogen-bond connectivity that renders proton transfer up to Y288 at the BNC feasible. No significant direct effect of the protonation state of one channel on the hydration level, hydrogen-bond connectivity, or interactions between protein residues in the other channel could be observed, rendering proton conductivity in the two channels independent of each other. Regulation of the order of proton uptake and proton passage in the two channels such that the “chemical” proton leaves its channel last must, therefore, be achieved by other means of communication, such as the location of the reducing electron.
en
dc.format.extent
32 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Cytochrome c Oxidase
en
dc.subject
protonation and hydration
en
dc.subject
molecular dynamics simulations
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::530 Physik::530 Physik
dc.title
Protonation-State Dependence of Hydration and Interactions in the Two Proton-Conducting Channels of Cytochrome c Oxidase
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
10464
dcterms.bibliographicCitation.doi
10.3390/ijms241310464
dcterms.bibliographicCitation.journaltitle
International Journal of Molecular Sciences
dcterms.bibliographicCitation.number
13
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
24
dcterms.bibliographicCitation.url
https://doi.org/10.3390/ijms241310464
refubium.affiliation
Physik
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
de
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1422-0067