Ligand-induced conformational dynamics of the Escherichia coli Na+ /H+ antiporter NhaA revealed by hydrogen/deuterium exchange mass spectrometry

Proceedings of the National Academy of Sciences of the United States of America
Martin Lorenz EisingerJulian David Langer

Abstract

Na+/H+ antiporters comprise a family of membrane proteins evolutionarily conserved in all kingdoms of life and play an essential role in cellular ion homeostasis. The NhaA crystal structure of Escherichia coli has become the paradigm for this class of secondary active transporters. However, structural data are only available at low pH, where NhaA is inactive. Here, we adapted hydrogen/deuterium-exchange mass spectrometry (HDX-MS) to analyze conformational changes in NhaA upon Li+ binding at physiological pH. Our analysis revealed a global conformational change in NhaA with two sets of movements around an immobile binding site. Based on these results, we propose a model for the ion translocation mechanism that explains previously controversial data for this antiporter. Furthermore, these findings contribute to our understanding of related human transporters that have been linked to various diseases.

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Sep 12, 2019·Physiological Reviews·S F Pedersen, L Counillon
Feb 8, 2019·The Journal of General Physiology·Vanessa LeoneLucy R Forrest
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Jun 30, 2018·The Journal of Physical Chemistry Letters·Esther S Brielle, Isaiah T Arkin

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