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

By Yandong Huang, Wei Chen, David L. Dotson, Oliver Beckstein and Jana Shen

Abstract

Data files to accompany the article in Nature Communications, in press.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

Publisher: 'Wiley'
Year: 2016
DOI identifier: 10.13016/M2VZ1F
OAI identifier: oai:drum.lib.umd.edu:1903/18477
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