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Structural basis for hepatitis B virus restriction by a viral receptor homologue

Author

Listed:
  • Kaho Shionoya

    (National Institute of Infectious Diseases
    Tokyo University of Science
    National Institute of Infectious Diseases)

  • Jae-Hyun Park

    (Yokohama City University
    Sungkyunkwan University School of Medicine)

  • Toru Ekimoto

    (Yokohama City University)

  • Junko S. Takeuchi

    (National Center for Global Health and Medicine)

  • Junki Mifune

    (National Institute of Infectious Diseases)

  • Takeshi Morita

    (National Institute of Infectious Diseases)

  • Naito Ishimoto

    (Yokohama City University)

  • Haruka Umezawa

    (Yokohama City University)

  • Kenichiro Yamamoto

    (Yokohama City University)

  • Chisa Kobayashi

    (National Institute of Infectious Diseases
    Tokyo University of Science
    National Institute of Infectious Diseases)

  • Atsuto Kusunoki

    (National Institute of Infectious Diseases)

  • Norimichi Nomura

    (Kyoto University)

  • So Iwata

    (Kyoto University
    RIKEN SPring-8 Center)

  • Masamichi Muramatsu

    (National Institute of Infectious Diseases
    Foundation for Biomedical Research and Innovation at Kobe)

  • Jeremy R. H. Tame

    (Yokohama City University)

  • Mitsunori Ikeguchi

    (Yokohama City University
    RIKEN)

  • Sam-Yong Park

    (Yokohama City University)

  • Koichi Watashi

    (National Institute of Infectious Diseases
    Tokyo University of Science
    National Institute of Infectious Diseases)

Abstract

Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP. Cell-based mutation analysis confirms that only Gly158 permitted preS1 binding, in contrast to robust bile acid transport among mutations. As the second determinant, Asn86 on the extracellular surface of mNTCP shows less capacity to restrain preS1 from dynamic fluctuation than Lys86 of hNTCP, resulting in unstable preS1 binding. Additionally, presence of long-chain conjugated-bile acids in the tunnel induces steric hindrance with preS1 through their tailed-chain. This study presents structural basis in which multiple sites in mNTCP constitute a molecular barrier to strictly restrict HBV.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53533-6
    DOI: 10.1038/s41467-024-53533-6
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    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. Nien-Jen Hu & So Iwata & Alexander D. Cameron & David Drew, 2011. "Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT," Nature, Nature, vol. 478(7369), pages 408-411, October.
    3. 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.
    4. Takahiro Muraoka & Daiki Noguchi & Rinshi S. Kasai & Kohei Sato & Ryo Sasaki & Kazuhito V. Tabata & Toru Ekimoto & Mitsunori Ikeguchi & Kiyoto Kamagata & Norihisa Hoshino & Hiroyuki Noji & Tomoyuki Ak, 2020. "A synthetic ion channel with anisotropic ligand response," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    5. Kapil Goutam & Francesco S. Ielasi & Els Pardon & Jan Steyaert & Nicolas Reyes, 2022. "Structural basis of sodium-dependent bile salt uptake into the liver," Nature, Nature, vol. 606(7916), pages 1015-1020, June.
    6. Benjamin J. Burwitz & Jochen M. Wettengel & Martin A. Mück-Häusl & Marc Ringelhan & Chunkyu Ko & Marvin M. Festag & Katherine B. Hammond & Mina Northrup & Benjamin N. Bimber & Thomas Jacob & Jason S. , 2017. "Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    7. Jinta Asami & Kanako Terakado Kimura & Yoko Fujita-Fujiharu & Hanako Ishida & Zhikuan Zhang & Yayoi Nomura & Kehong Liu & Tomoko Uemura & Yumi Sato & Masatsugu Ono & Masaki Yamamoto & Takeshi Noda & H, 2022. "Structure of the bile acid transporter and HBV receptor NTCP," Nature, Nature, vol. 606(7916), pages 1021-1026, June.
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