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

Autor:	Eisinger ML; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany., Dörrbaum AR; Department of Synaptic Plasticity, Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany., Michel H; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany; hartmut.michel@biophys.mpg.de etana.padan@mail.huji.ac.il julian.langer@biophys.mpg.de., Padan E; Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel hartmut.michel@biophys.mpg.de etana.padan@mail.huji.ac.il julian.langer@biophys.mpg.de., Langer JD; Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany; hartmut.michel@biophys.mpg.de etana.padan@mail.huji.ac.il julian.langer@biophys.mpg.de.; Department of Synaptic Plasticity, Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Oct 31; Vol. 114 (44), pp. 11691-11696. Date of Electronic Publication: 2017 Oct 16.
DOI:	10.1073/pnas.1703422114
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. (Published under the PNAS license.)
Databáze:	MEDLINE
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