IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v606y2022i7916d10.1038_s41586-022-04857-0.html
   My bibliography  Save this article

Structural insights into the HBV receptor and bile acid transporter NTCP

Author

Listed:
  • Jae-Hyun Park

    (Yokohama City University)

  • Masashi Iwamoto

    (National Institute of Infectious Diseases)

  • Ji-Hye Yun

    (Yonsei University
    PCG-Biotech)

  • Tomomi Uchikubo-Kamo

    (RIKEN Center for Biosystems Dynamics Research)

  • Donghwan Son

    (Yonsei University)

  • Zeyu Jin

    (Yokohama City University
    Yonsei University)

  • Hisashi Yoshida

    (Yokohama City University)

  • Mio Ohki

    (Yokohama City University)

  • Naito Ishimoto

    (Yokohama City University)

  • Kenji Mizutani

    (Yokohama City University)

  • Mizuki Oshima

    (National Institute of Infectious Diseases
    Tokyo University of Science)

  • Masamichi Muramatsu

    (National Institute of Infectious Diseases)

  • Takaji Wakita

    (National Institute of Infectious Diseases)

  • Mikako Shirouzu

    (RIKEN Center for Biosystems Dynamics Research)

  • Kehong Liu

    (Kyoto University)

  • Tomoko Uemura

    (Kyoto University)

  • Norimichi Nomura

    (Kyoto University)

  • So Iwata

    (Kyoto University
    RIKEN SPring-8 Center)

  • Koichi Watashi

    (National Institute of Infectious Diseases
    Tokyo University of Science
    Research Center for Drug and Vaccine Development)

  • Jeremy R. H. Tame

    (Yokohama City University)

  • Tomohiro Nishizawa

    (Yokohama City University)

  • Weontae Lee

    (Yonsei University
    PCG-Biotech)

  • Sam-Yong Park

    (Yokohama City University)

Abstract

Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein3. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria4,5, and these models are believed to resemble closely both NTCP and ASBT. Here we have used cryo-electron microscopy to solve the structure of NTCP bound to an antibody, clearly showing that the transporter has no equivalent of the first transmembrane helix found in other SLC10 proteins, and that the N terminus is exposed on the extracellular face. Comparison of our structure with those of related proteins indicates a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1, presenting new opportunities for structure-based drug design.

Suggested Citation

  • Jae-Hyun Park & Masashi Iwamoto & Ji-Hye Yun & Tomomi Uchikubo-Kamo & Donghwan Son & Zeyu Jin & Hisashi Yoshida & Mio Ohki & Naito Ishimoto & Kenji Mizutani & Mizuki Oshima & Masamichi Muramatsu & Tak, 2022. "Structural insights into the HBV receptor and bile acid transporter NTCP," Nature, Nature, vol. 606(7916), pages 1027-1031, June.
    • Handle: RePEc:nat:nature:v:606:y:2022:i:7916:d:10.1038_s41586-022-04857-0
    DOI: 10.1038/s41586-022-04857-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-04857-0
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-022-04857-0?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Yongzhen Liu & Thomas R. Cafiero & Debby Park & Abhishek Biswas & Benjamin Y. Winer & Cheul H. Cho & Yaron Bram & Vasuretha Chandar & Aoife K. O’ Connell & Hans P. Gertje & Nicholas Crossland & Robert, 2023. "Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Kaho Shionoya & Jae-Hyun Park & Toru Ekimoto & Junko S. Takeuchi & Junki Mifune & Takeshi Morita & Naito Ishimoto & Haruka Umezawa & Kenichiro Yamamoto & Chisa Kobayashi & Atsuto Kusunoki & Norimichi , 2024. "Structural basis for hepatitis B virus restriction by a viral receptor homologue," Nature Communications, Nature, vol. 15(1), pages 1-15, 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:nature:v:606:y:2022:i:7916:d:10.1038_s41586-022-04857-0. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.