pH- and sodium-induced changes in a sodium/proton antiporter
Cristina Paulino1, Werner Kühlbrandt
1Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
Elife
|January 30, 2014
Summary
This study reveals how the archaeal sodium-hydrogen antiporter MjNhaP1 changes shape to transport ions. Sodium binding, not pH, drives conformational changes essential for Na+/H+ antiport.
Area of Science:
- Biochemistry
- Structural Biology
- Membrane Transport
Background:
- MjNhaP1 is an archaeal electroneutral sodium/hydrogen antiporter.
- It shares structural and functional similarities with the human sodium/hydrogen exchanger 1 (NHE1).
- Understanding its mechanism provides insights into human ion transport.
Purpose of the Study:
- To investigate substrate-induced conformational changes in MjNhaP1.
- To elucidate the role of pH and sodium concentration in MjNhaP1 function.
- To determine the structural basis of Na+/H+ antiport.
Main Methods:
- Electron crystallography of 2D crystals of MjNhaP1.
- Experiments conducted under varying physiological pH and sodium concentrations.
- Analysis of projection difference maps and determination of dissociation constants.
Main Results:
- Conformational changes were primarily driven by sodium concentration, largely independent of pH.
- Apparent dissociation constants showed significantly stronger Na+ binding at pH 8 compared to pH 4.
- Projection difference maps revealed helix movements of approximately 2 Å in the ion translocation region.
Conclusions:
- Proposed mechanism involves conformational shifts converting the antiporter between proton-bound, outward-open and Na+-bound, inward-open states.
- These state oscillations facilitate rapid Na+/H+ antiport.
- The findings offer a structural perspective on electroneutral cation/proton exchange mechanisms.
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