Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter

  1. Julia Steiner
  2. Leonid Sazanov  Is a corresponding author
  1. Institute of Science and Technology Austria, Austria

Abstract

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.

Data availability

Structure of the Mrp dimer is deposited in PDB with PDB ID 6Z16, with corresponding cryo-EM density maps in EMDB (EMD-11027).

The following data sets were generated

Article and author information

Author details

  1. Julia Steiner

    Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Leonid Sazanov

    Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    sazanov@ist.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0977-7989

Funding

Austrian Academy of Sciences (DOC fellowship)

  • Julia Steiner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sriram Subramaniam, University of British Columbia, Canada

Publication history

  1. Received: May 28, 2020
  2. Accepted: July 30, 2020
  3. Accepted Manuscript published: July 31, 2020 (version 1)
  4. Version of Record published: August 11, 2020 (version 2)

Copyright

© 2020, Steiner & Sazanov

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Julia Steiner
  2. Leonid Sazanov
(2020)
Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter
eLife 9:e59407.
https://doi.org/10.7554/eLife.59407

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