Structure and transport mechanism of the sodium/protonantiporter MjNhaP1

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Abstract

Sodium/proton antiporters are essential for sodium and pH homeostasis and play a major role in human health and disease. We determined the structures of the archaeal sodium/proton antiporter MjNhaP1 in two complementary states. The inward-open state was obtained by x-ray crystallography in the presence of sodium at pH8, where the transporter is highly active. The outward-open state was obtained by electron crystallography without sodium at pH4, where MjNhaP1 is inactive. Comparison of both structures reveals a 7{degree sign} tilt of the 6 helix bundle. ²²Na⁺ uptake measurements indicate non-cooperative transport with an activity maximum at pH7.5. We conclude that binding of a Na⁺ ion from the outside induces helix movements that close the extracellular cavity, open the cytoplasmic funnel, and result in a ~5 Å vertical relocation of the ion binding site to release the substrate ion into the cytoplasm.

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Cristina Paulino

Max Planck Institute of Biophysics, Frankfurt am Main, Germany

Competing interests
No competing interests declared.
David Wöhlert

Max Planck Institute of Biophysics, Frankfurt am Main, Germany

Competing interests
No competing interests declared.
Ekaterina Kapotova

Max Planck Institute of Biophysics, Frankfurt am Main, Germany

Competing interests
No competing interests declared.
Özkan Yildiz

Max Planck Institute of Biophysics, Frankfurt am Main, Germany

For correspondence
Oezkan.Yildiz@biophys.mpg.de

Competing interests
No competing interests declared.
Werner Kühlbrandt

Max Planck Institute of Biophysics, Frankfurt am Main, Germany

Competing interests
Werner Kühlbrandt, Reviewing editor, eLife.

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