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PH- and sodium-induced changes in a sodium/proton antiporter.

ABSTRACT: We examined substrate-induced conformational changes in MjNhaP1, an archaeal electroneutral Na(+)/H(+)-antiporter resembling the human antiporter NHE1, by electron crystallography of 2D crystals in a range of physiological pH and Na(+) conditions. In the absence of sodium, changes in pH had no major effect. By contrast, changes in Na(+) concentration caused a marked conformational change that was largely pH-independent. Crystallographically determined, apparent dissociation constants indicated ?10-fold stronger Na(+) binding at pH 8 than at pH 4, consistent with substrate competition for a common ion-binding site. Projection difference maps indicated helix movements by about 2 Å in the 6-helix bundle region of MjNhaP1 that is thought to contain the ion translocation site. We propose that these movements convert the antiporter from the proton-bound, outward-open state to the Na(+)-bound, inward-open state. Oscillation between the two states would result in rapid Na(+)/H(+) antiport. DOI: http://dx.doi.org/10.7554/eLife.01412.001.

SUBMITTER: Paulino C

PROVIDER: S-EPMC3900740 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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pH- and sodium-induced changes in a sodium/proton antiporter.

Paulino Cristina C Kühlbrandt Werner W

eLife 20140128

We examined substrate-induced conformational changes in MjNhaP1, an archaeal electroneutral Na(+)/H(+)-antiporter resembling the human antiporter NHE1, by electron crystallography of 2D crystals in a range of physiological pH and Na(+) conditions. In the absence of sodium, changes in pH had no major effect. By contrast, changes in Na(+) concentration caused a marked conformational change that was largely pH-independent. Crystallographically determined, apparent dissociation constants indicated ∼ ...[more]

PMID: 24473071

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