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

Sauer, David, Marden, Jennifer, Sudar, Joseph, Song, Jinmei, Christopher, Mulligan, Wang, Da-Neng (2022) Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY. Nature Communications, 13 (1). Article Number 2644. ISSN 2041-1723. (doi:10.1038/s41467-022-30406-4) (KAR id:95499)


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.

Item Type: Article
DOI/Identification number: 10.1038/s41467-022-30406-4
Subjects: Q Science
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Christopher Mulligan
Date Deposited: 20 Jun 2022 12:38 UTC
Last Modified: 21 Jun 2022 10:40 UTC
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University of Kent Author Information

Christopher, Mulligan.

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