Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements.
This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank Dr Victor-Valentin Hodirnau and Daniel Johann Gütl from IST Austria for assistance with collecting cryo-EM data. We thank Prof. Masahiro Ito (Graduate School of Life Sciences, Toyo University, Japan) for a kind provision of plasmid DNA encoding Mrp from A. flavithermus WK1. JS is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria.
Steiner J, Sazanov LA. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 2020;9. doi:10.7554/eLife.59407
Steiner, J., & Sazanov, L. A. (2020). Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. ELife, 9. https://doi.org/10.7554/eLife.59407
Steiner, Julia, and Leonid A Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” ELife 9 (2020). https://doi.org/10.7554/eLife.59407.
J. Steiner and L. A. Sazanov, “Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter,” eLife, vol. 9, 2020.
Steiner J, Sazanov LA. 2020. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 9.
Steiner, Julia, and Leonid A. Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” ELife, vol. 9, e59407, eLife Sciences Publications, 2020, doi:10.7554/eLife.59407.
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