Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA
Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA
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Date
2016
Authors
Huang, Yandong
Chen, Wei
Dotson, David L.
Beckstein, Oliver
Shen, Jana
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Abstract
Escherichia 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.
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Data files to accompany the article in Nature Communications, in press.