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Broad phylogenetic analysis of cation/proton antiporters reveals transport determinants

Author

Listed:
  • Gal Masrati

    (Tel-Aviv University)

  • Manish Dwivedi

    (The Hebrew University of Jerusalem)

  • Abraham Rimon

    (The Hebrew University of Jerusalem)

  • Yael Gluck-Margolin

    (The Hebrew University of Jerusalem)

  • Amit Kessel

    (Tel-Aviv University)

  • Haim Ashkenazy

    (Tel-Aviv University)

  • Itay Mayrose

    (Tel-Aviv University)

  • Etana Padan

    (The Hebrew University of Jerusalem)

  • Nir Ben-Tal

    (Tel-Aviv University)

Abstract

Cation/proton antiporters (CPAs) play a major role in maintaining living cells’ homeostasis. CPAs are commonly divided into two main groups, CPA1 and CPA2, and are further characterized by two main phenotypes: ion selectivity and electrogenicity. However, tracing the evolutionary relationships of these transporters is challenging because of the high diversity within CPAs. Here, we conduct comprehensive evolutionary analysis of 6537 representative CPAs, describing the full complexity of their phylogeny, and revealing a sequence motif that appears to determine central phenotypic characteristics. In contrast to previous suggestions, we show that the CPA1/CPA2 division only partially correlates with electrogenicity. Our analysis further indicates two acidic residues in the binding site that carry the protons in electrogenic CPAs, and a polar residue in the unwound transmembrane helix 4 that determines ion selectivity. A rationally designed triple mutant successfully converted the electrogenic CPA, EcNhaA, to be electroneutral.

Suggested Citation

  • Gal Masrati & Manish Dwivedi & Abraham Rimon & Yael Gluck-Margolin & Amit Kessel & Haim Ashkenazy & Itay Mayrose & Etana Padan & Nir Ben-Tal, 2018. "Broad phylogenetic analysis of cation/proton antiporters reveals transport determinants," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06770-5
    DOI: 10.1038/s41467-018-06770-5
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    Cited by:

    1. Josep Vilarrasa-Blasi & Tamara Vellosillo & Robert E. Jinkerson & Friedrich Fauser & Tingting Xiang & Benjamin B. Minkoff & Lianyong Wang & Kiril Kniazev & Michael Guzman & Jacqueline Osaki & Gregory , 2024. "Multi-omics analysis of green lineage osmotic stress pathways unveils crucial roles of different cellular compartments," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Yuhang Wang & Chengcai Pan & Qihao Chen & Qing Xie & Yiwei Gao & Lingli He & Yue Li & Yanli Dong & Xingyu Jiang & Yan Zhao, 2023. "Architecture and autoinhibitory mechanism of the plasma membrane Na+/H+ antiporter SOS1 in Arabidopsis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Ashutosh Gulati & Surabhi Kokane & Annemarie Perez-Boerema & Claudia Alleva & Pascal F. Meier & Rei Matsuoka & David Drew, 2024. "Structure and mechanism of the K+/H+ exchanger KefC," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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