IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30406-4.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30406-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30406-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Martin F. Peter & Jan A. Ruland & Yeojin Kim & Philipp Hendricks & Niels Schneberger & Jan Peter Siebrasse & Gavin H. Thomas & Ulrich Kubitscheck & Gregor Hagelueken, 2024. "Conformational coupling of the sialic acid TRAP transporter HiSiaQM with its substrate binding protein HiSiaP," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Anna M. Borowska & Maria Gabriella Chiariello & Alisa A. Garaeva & Jan Rheinberger & Siewert J. Marrink & Cristina Paulino & Dirk J. Slotboom, 2024. "Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Takafumi Kato & Tsukasa Kusakizako & Chunhuan Jin & Xinyu Zhou & Ryuichi Ohgaki & LiLi Quan & Minhui Xu & Suguru Okuda & Kan Kobayashi & Keitaro Yamashita & Tomohiro Nishizawa & Yoshikatsu Kanai & Osa, 2022. "Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Zhenglai Zhang & Huiwen Chen & Ze Geng & Zhuoya Yu & Hang Li & Yanli Dong & Hongwei Zhang & Zhuo Huang & Juquan Jiang & Yan Zhao, 2022. "Structural basis of ligand binding modes of human EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Emanuela Colucci & Zaid R. Anshari & Miyer F. Patiño-Ruiz & Mariia Nemchinova & Jacob Whittaker & Dirk J. Slotboom & Albert Guskov, 2023. "Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. Martin F. Peter & Jan A. Ruland & Peer Depping & Niels Schneberger & Emmanuele Severi & Jonas Moecking & Karl Gatterdam & Sarah Tindall & Alexandre Durand & Veronika Heinz & Jan Peter Siebrasse & Paul, 2022. "Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Biao Qiu & Olga Boudker, 2023. "Symport and antiport mechanisms of human glutamate transporters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. James S. Davies & Michael J. Currie & Rachel A. North & Mariafrancesca Scalise & Joshua D. Wright & Jack M. Copping & Daniela M. Remus & Ashutosh Gulati & Dustin R. Morado & Sam A. Jamieson & Michael , 2023. "Structure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. 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.
    9. Yao Zhang & Yuhan Jiang & Kaifu Gao & Dexin Sui & Peixuan Yu & Min Su & Guo-Wei Wei & Jian Hu, 2023. "Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Gabriel Núñez-Vivanco & Angélica Fierro & Pablo Moya & Patricio Iturriaga-Vásquez & Miguel Reyes-Parada, 2018. "3D similarities between the binding sites of monoaminergic target proteins," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-18, July.
    11. Weiqi Zhang & Dian Ding & Yishuo Lu & Hongyi Chen & Peijun Jiang & Peng Zuo & Guangxi Wang & Juan Luo & Yue Yin & Jianyuan Luo & Yuxin Yin, 2024. "Structural and functional insights into the lipid regulation of human anion exchanger 2," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    12. Hyun Deok Song & Fangqiang Zhu, 2015. "Conformational Changes in Two Inter-Helical Loops of Mhp1 Membrane Transporter," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-19, July.
    13. Lilia Leisle & Kin Lam & Sepehr Dehghani-Ghahnaviyeh & Eva Fortea & Jason D. Galpin & Christopher A. Ahern & Emad Tajkhorshid & Alessio Accardi, 2022. "Backbone amides are determinants of Cl− selectivity in CLC ion channels," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Solveig G. Schmidt & Mette Galsgaard Malle & Anne Kathrine Nielsen & Søren S.-R. Bohr & Ciara F. Pugh & Jeppe C. Nielsen & Ida H. Poulsen & Kasper D. Rand & Nikos S. Hatzakis & Claus J. Loland, 2022. "The dopamine transporter antiports potassium to increase the uptake of dopamine," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. 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.
    16. Daniela Skálová & Jana Zídková & Stanislav Voháňka & Radim Mazanec & Zuzana Mušová & Petr Vondráček & Lenka Mrázová & Josef Kraus & Kamila Réblová & Lenka Fajkusová, 2013. "CLCN1 Mutations in Czech Patients with Myotonia Congenita, In Silico Analysis of Novel and Known Mutations in the Human Dimeric Skeletal Muscle Chloride Channel," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-1, December.
    17. Chancievan Thangaratnarajah & Mark Nijland & Luís Borges-Araújo & Aike Jeucken & Jan Rheinberger & Siewert J. Marrink & Paulo C. T. Souza & Cristina Paulino & Dirk J. Slotboom, 2023. "Expulsion mechanism of the substrate-translocating subunit in ECF transporters," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Qing Zhang & Liyan Jian & Deqiang Yao & Bing Rao & Ying Xia & Kexin Hu & Shaobai Li & Yafeng Shen & Mi Cao & An Qin & Jie Zhao & Yu Cao, 2023. "The structural basis of the pH-homeostasis mediated by the Cl−/HCO3− exchanger, AE2," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    19. Yishuo Lu & Peng Zuo & Hongyi Chen & Hui Shan & Weize Wang & Zonglin Dai & He Xu & Yayu Chen & Ling Liang & Dian Ding & Yan Jin & Yuxin Yin, 2023. "Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP2," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    20. Zhao Yang & Xue Zhang & Shiwei Ye & Jingtao Zheng & Xiaowei Huang & Fang Yu & Zhenguo Chen & Shiqing Cai & Peng Zhang, 2023. "Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30406-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.