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

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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

1. Steiner J
2. Sazanov LA
(2020) Structure of the Mrp antiporter complex
Protein Data Bank, ID 6Z16.

https://www.rcsb.org/structure/6Z16
1. Steiner J
2. Sazanov LA
(2020) Structure of the Mrp antiporter complex
Electron Microscopy Data Bank, EMD-11027.

https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-11027

Article and author information

Author details

Julia Steiner

Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.