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Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY

Author

Listed:
  • David B. Sauer

    (New York University School of Medicine
    New York University School of Medicine
    University of Oxford)

  • Jennifer J. Marden

    (New York University School of Medicine
    New York University School of Medicine)

  • Joseph C. Sudar

    (New York University School of Medicine)

  • Jinmei Song

    (New York University School of Medicine
    New York University School of Medicine)

  • Christopher Mulligan

    (University of Kent, Canterbury)

  • Da-Neng Wang

    (New York University School of Medicine
    New York University School of Medicine)

Abstract

The Na+-dependent dicarboxylate transporter from Vibrio cholerae (VcINDY) is a prototype for the divalent anion sodium symporter (DASS) family. While the utilization of an electrochemical Na+ gradient to power substrate transport is well established for VcINDY, the structural basis of this coupling between sodium and substrate binding is not currently understood. Here, using a combination of cryo-EM structure determination, succinate binding and site-directed cysteine alkylation assays, we demonstrate that the VcINDY protein couples sodium- and substrate-binding via a previously unseen cooperative mechanism by conformational selection. In the absence of sodium, substrate binding is abolished, with the succinate binding regions exhibiting increased flexibility, including HPinb, TM10b and the substrate clamshell motifs. Upon sodium binding, these regions become structurally ordered and create a proper binding site for the substrate. Taken together, these results provide strong evidence that VcINDY’s conformational selection mechanism is a result of the sodium-dependent formation of the substrate binding site.

Suggested Citation

  • David B. Sauer & Jennifer J. Marden & Joseph C. Sudar & Jinmei Song & Christopher Mulligan & Da-Neng Wang, 2022. "Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30406-4
    DOI: 10.1038/s41467-022-30406-4
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    1. Guus B. Erkens & Inga Hänelt & Joris M. H. Goudsmits & Dirk Jan Slotboom & Antoine M. van Oijen, 2013. "Unsynchronised subunit motion in single trimeric sodium-coupled aspartate transporters," Nature, Nature, vol. 502(7469), pages 119-123, October.
    2. Olga Boudker & Renae M. Ryan & Dinesh Yernool & Keiko Shimamoto & Eric Gouaux, 2007. "Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter," Nature, Nature, vol. 445(7126), pages 387-393, January.
    3. Atsuko Yamashita & Satinder K. Singh & Toshimitsu Kawate & Yan Jin & Eric Gouaux, 2005. "Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters," Nature, Nature, vol. 437(7056), pages 215-223, September.
    4. Dinesh Yernool & Olga Boudker & Yan Jin & Eric Gouaux, 2004. "Structure of a glutamate transporter homologue from Pyrococcus horikoshii," Nature, Nature, vol. 431(7010), pages 811-818, October.
    5. Raimund Dutzler & Ernest B. Campbell & Martine Cadene & Brian T. Chait & Roderick MacKinnon, 2002. "X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity," Nature, Nature, vol. 415(6869), pages 287-294, January.
    6. Romina Mancusso & G. Glenn Gregorio & Qun Liu & Da-Neng Wang, 2012. "Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter," Nature, Nature, vol. 491(7425), pages 622-626, November.
    7. Valentina Arkhipova & Albert Guskov & Dirk J. Slotboom, 2020. "Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    8. Kevin W. Huynh & Jiansen Jiang & Natalia Abuladze & Kirill Tsirulnikov & Liyo Kao & Xuesi Shao & Debra Newman & Rustam Azimov & Alexander Pushkin & Z. Hong Zhou & Ira Kurtz, 2018. "CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    9. Nicolas Reyes & Christopher Ginter & Olga Boudker, 2009. "Transport mechanism of a bacterial homologue of glutamate transporters," Nature, Nature, vol. 462(7275), pages 880-885, December.
    10. David B. Sauer & Jinmei Song & Bing Wang & Jacob K. Hilton & Nathan K. Karpowich & Joseph A. Mindell & William J. Rice & Da-Neng Wang, 2021. "Structure and inhibition mechanism of the human citrate transporter NaCT," Nature, Nature, vol. 591(7848), pages 157-161, March.
    11. Rongxin Nie & Steven Stark & Jindrich Symersky & Ronald S. Kaplan & Min Lu, 2017. "Structure and function of the divalent anion/Na+ symporter from Vibrio cholerae and a humanized variant," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
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