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Structure and transport mechanism of the sodium/proton antiporter MjNhaP1.

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 pH 8, where the transporter is highly active. The outward-open state was obtained by electron crystallography without sodium at pH 4, where MjNhaP1 is inactive. Comparison of both structures reveals a 7° tilt of the 6 helix bundle. (22)Na(+) uptake measurements indicate non-cooperative transport with an activity maximum at pH 7.5. 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.

SUBMITTER: Paulino C

PROVIDER: S-EPMC4381896 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Structure and transport mechanism of the sodium/proton antiporter MjNhaP1.

Paulino Cristina C Wöhlert David D Kapotova Ekaterina E Yildiz Özkan Ö Kühlbrandt Werner W

eLife 20141126

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 pH 8, where the transporter is highly active. The outward-open state was obtained by electron crystallography without sodium at pH 4, where MjNhaP1 is inactive. Comparison of both str ...[more]

PMID: 25426803

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