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Yokohama City University

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Nat. Struct. Mol. Biol., Jan 17 2024, | https://doi.org/10.1038/s41594-023-01191-5 Structural basis of hepatitis B virus receptor binding

Jinta Asami^1,8, Jae-Hyun Park^2,8, Yayoi Nomura^3,8, Chisa Kobayashi^4,5,8, Junki Mifune⁶, Naito Ishimoto², Tomoko Uemura³, Kehong Liu³, Yumi Sato³, Zhikuan Zhang¹, Masamichi Muramatsu⁴, Takaji Wakita⁴, David Drew⁷, So Iwata³, Toshiyuki Shimizu¹, Koichi Watashi^4,5,6, Sam-Yong Park², Norimichi Nomura³ & Umeharu Ohto¹

¹Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

²Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.

³Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

⁴Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

⁵Department of Applied Biological Science, Tokyo University of Science, Noda, Japan.

⁶Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.

⁷Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.

⁸These authors contributed equally: Jinta Asami, Jae-Hyun Park, Yayoi Nomura, Chisa Kobayashi.

Corresponding authors: Correspondence to Koichi Watashi, Sam-Yong Park, Norimichi Nomura or Umeharu Ohto.

Abstract

Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus-host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-19)
연구진국외 연구진
분야 생명과학 > 생화학

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