IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49899-2.html
   My bibliography  Save this article

Dimeric transport mechanism of human vitamin C transporter SVCT1

Author

Listed:
  • Takaaki A. Kobayashi

    (The University of Tokyo)

  • Hiroto Shimada

    (The University of Tokyo
    Chugai Pharmaceutical Co., Ltd.)

  • Fumiya K. Sano

    (The University of Tokyo)

  • Yuzuru Itoh

    (The University of Tokyo)

  • Sawako Enoki

    (The University of Tokyo)

  • Yasushi Okada

    (The University of Tokyo
    The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research (BDR)
    The University of Tokyo)

  • Tsukasa Kusakizako

    (The University of Tokyo)

  • Osamu Nureki

    (The University of Tokyo)

Abstract

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5–3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49899-2
    DOI: 10.1038/s41467-024-49899-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49899-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-49899-2?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. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Haon Futamata & Masahiro Fukuda & Rie Umeda & Keitaro Yamashita & Atsuhiro Tomita & Satoe Takahashi & Takafumi Shikakura & Shigehiko Hayashi & Tsukasa Kusakizako & Tomohiro Nishizawa & Kazuaki Homma &, 2022. "Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Kallol Gupta & Joseph A. C. Donlan & Jonathan T. S. Hopper & Povilas Uzdavinys & Michael Landreh & Weston B. Struwe & David Drew & Andrew J. Baldwin & Phillip J. Stansfeld & Carol V. Robinson, 2017. "The role of interfacial lipids in stabilizing membrane protein oligomers," Nature, Nature, vol. 541(7637), pages 421-424, January.
    4. Feiran Lu & Shuo Li & Yang Jiang & Jing Jiang & He Fan & Guifeng Lu & Dong Deng & Shangyu Dang & Xu Zhang & Jiawei Wang & Nieng Yan, 2011. "Structure and mechanism of the uracil transporter UraA," Nature, Nature, vol. 472(7342), pages 243-246, April.
    5. 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.
    6. Hiroyasu Tsukaguchi & Taro Tokui & Bryan Mackenzie & Urs V. Berger & Xing-Zhen Chen & Yangxi Wang & Richard F. Brubaker & Matthias A. Hediger, 1999. "A family of mammalian Na+-dependent L-ascorbic acid transporters," Nature, Nature, vol. 399(6731), pages 70-75, May.
    7. 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.
    8. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    9. 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.
    10. Weiguang Wang & Kirill Tsirulnikov & Hristina R. Zhekova & Gülru Kayık & Hanif Muhammad Khan & Rustam Azimov & Natalia Abuladze & Liyo Kao & Debbie Newman & Sergei Yu. Noskov & Z. Hong Zhou & Alexande, 2021. "Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. Wenxin Hu & Alex Song & Hongjin Zheng, 2024. "Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    6. 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.
    7. 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.
    8. Ye Yuan & Lei Chen & Kexu Song & Miaomiao Cheng & Ling Fang & Lingfei Kong & Lanlan Yu & Ruonan Wang & Zhendong Fu & Minmin Sun & Qian Wang & Chengjun Cui & Haojue Wang & Jiuyang He & Xiaonan Wang & Y, 2024. "Stable peptide-assembled nanozyme mimicking dual antifungal actions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Ivica Odorčić & Mohamed Belal Hamed & Sam Lismont & Lucía Chávez-Gutiérrez & Rouslan G. Efremov, 2024. "Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Stella Vitt & Simone Prinz & Martin Eisinger & Ulrich Ermler & Wolfgang Buckel, 2022. "Purification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    11. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative AI," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, National Bureau of Economic Research, Inc.
    12. Riya Shah & Thomas C. Panagiotou & Gregory B. Cole & Trevor F. Moraes & Brigitte D. Lavoie & Christopher A. McCulloch & Andrew Wilde, 2024. "The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Yashan Yang & Qianqian Shao & Mingcheng Guo & Lin Han & Xinyue Zhao & Aohan Wang & Xiangyun Li & Bo Wang & Ji-An Pan & Zhenguo Chen & Andrei Fokine & Lei Sun & Qianglin Fang, 2024. "Capsid structure of bacteriophage ΦKZ provides insights into assembly and stabilization of jumbo phages," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    14. Bret M. Boyd & Ian James & Kevin P. Johnson & Robert B. Weiss & Sarah E. Bush & Dale H. Clayton & Colin Dale, 2024. "Stochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    16. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Shuo-Shuo Liu & Tian-Xia Jiang & Fan Bu & Ji-Lan Zhao & Guang-Fei Wang & Guo-Heng Yang & Jie-Yan Kong & Yun-Fan Qie & Pei Wen & Li-Bin Fan & Ning-Ning Li & Ning Gao & Xiao-Bo Qiu, 2024. "Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Justin N. Vaughn & Sandra E. Branham & Brian Abernathy & Amanda M. Hulse-Kemp & Adam R. Rivers & Amnon Levi & William P. Wechter, 2022. "Graph-based pangenomics maximizes genotyping density and reveals structural impacts on fungal resistance in melon," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    19. Eliza S. Nieweglowska & Axel F. Brilot & Melissa Méndez-Moran & Claire Kokontis & Minkyung Baek & Junrui Li & Yifan Cheng & David Baker & Joseph Bondy-Denomy & David A. Agard, 2023. "The ϕPA3 phage nucleus is enclosed by a self-assembling 2D crystalline lattice," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    20. Sash Lopaticki & Robyn McConville & Alan John & Niall Geoghegan & Shihab Deen Mohamed & Lisa Verzier & Ryan W. J. Steel & Cindy Evelyn & Matthew T. O’Neill & Niccolay Madiedo Soler & Nichollas E. Scot, 2022. "Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission," Nature Communications, Nature, vol. 13(1), pages 1-18, 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:15:y:2024:i:1:d:10.1038_s41467-024-49899-2. 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.