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Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity

Author

Listed:
  • Yilmaz Alguel

    (Imperial College London)

  • Sotiris Amillis

    (Faculty of Biology, University of Athens)

  • James Leung

    (Imperial College London)

  • George Lambrinidis

    (Faculty of Pharmacy, University of Athens)

  • Stefano Capaldi

    (Imperial College London
    University of Verona)

  • Nicola J. Scull

    (Imperial College London)

  • Gregory Craven

    (Imperial College London)

  • So Iwata

    (Imperial College London
    JST, Research Acceleration Program, Membrane Protein Crystallography Project)

  • Alan Armstrong

    (Imperial College London)

  • Emmanuel Mikros

    (Faculty of Pharmacy, University of Athens)

  • George Diallinas

    (Faculty of Biology, University of Athens)

  • Alexander D. Cameron

    (School of Life Sciences, University of Warwick)

  • Bernadette Byrne

    (Imperial College London)

Abstract

The uric acid/xanthine H+ symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1–11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin.

Suggested Citation

  • Yilmaz Alguel & Sotiris Amillis & James Leung & George Lambrinidis & Stefano Capaldi & Nicola J. Scull & Gregory Craven & So Iwata & Alan Armstrong & Emmanuel Mikros & George Diallinas & Alexander D. , 2016. "Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11336
    DOI: 10.1038/ncomms11336
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    Cited by:

    1. Mingxing Wang & Jin He & Shanshan Li & Qianwen Cai & Kaiming Zhang & Ji She, 2023. "Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    2. Takaaki A. Kobayashi & Hiroto Shimada & Fumiya K. Sano & Yuzuru Itoh & Sawako Enoki & Yasushi Okada & Tsukasa Kusakizako & Osamu Nureki, 2024. "Dimeric transport mechanism of human vitamin C transporter SVCT1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Benedikt T. Kuhn & Jonathan Zöller & Iwan Zimmermann & Tim Gemeinhardt & Dogukan H. Özkul & Julian D. Langer & Markus A. Seeger & Eric R. Geertsma, 2024. "Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Lie Wang & Anthony Hoang & Eva Gil-Iturbe & Arthur Laganowsky & Matthias Quick & Ming Zhou, 2024. "Mechanism of anion exchange and small-molecule inhibition of pendrin," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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