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Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA

dc.contributor.authorHuang, Yandong
dc.contributor.authorChen, Wei
dc.contributor.authorDotson, David L.
dc.contributor.authorBeckstein, Oliver
dc.contributor.authorShen, Jana
dc.descriptionData files to accompany the article in Nature Communications, in press.en_US
dc.description.abstractEscherichia coli NhaA is a prototype sodium-proton antiporter, which has been extensively characterized by X-ray crystallography, biochemical and biophysical experiments. However, the identities of proton carriers and details of pH-regulated mechanism remain controversial. Here we report constant pH molecular dynamics data, which reveal that NhaA activation involves a net charge switch of a pH sensor at the entrance of the cytoplasmic funnel and opening of a hydrophobic gate at the end of the funnel. The latter is triggered by charging of Asp164, the first proton carrier. The second proton carrier Lys300 forms a salt bridge with Asp163 in the inactive state, and releases a proton when a sodium ion binds Asp163. These data reconcile current models and illustrate the power of state-of-the-art molecular dynamics simulations in providing atomic details of proton-coupled transport across membrane, which is challenging to elucidate by experimental techniques.en_US
dc.titleMechanism of pH-dependent activation of the sodium-proton antiporter NhaAen_US
dc.relation.isAvailableAtA. James Clark School of Engineeringen_us
dc.relation.isAvailableAtFischell Department of Bioengineeringen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us

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