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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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    References listed on IDEAS

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