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Structural insights into the HBV receptor and bile acid transporter NTCP.
Park, Jae-Hyun; Iwamoto, Masashi; Yun, Ji-Hye; Uchikubo-Kamo, Tomomi; Son, Donghwan; Jin, Zeyu; Yoshida, Hisashi; Ohki, Mio; Ishimoto, Naito; Mizutani, Kenji; Oshima, Mizuki; Muramatsu, Masamichi; Wakita, Takaji; Shirouzu, Mikako; Liu, Kehong; Uemura, Tomoko; Nomura, Norimichi; Iwata, So; Watashi, Koichi; Tame, Jeremy R H; Nishizawa, Tomohiro; Lee, Weontae; Park, Sam-Yong.
Afiliación
  • Park JH; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Iwamoto M; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
  • Yun JH; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
  • Uchikubo-Kamo T; PCG-Biotech, Seoul, South Korea.
  • Son D; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan.
  • Jin Z; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
  • Yoshida H; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Ohki M; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
  • Ishimoto N; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Mizutani K; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Oshima M; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Muramatsu M; Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
  • Wakita T; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
  • Shirouzu M; Department of Biological Sciences, Tokyo University of Science, Noda, Japan.
  • Liu K; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
  • Uemura T; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
  • Nomura N; Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan.
  • Iwata S; Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Watashi K; Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Tame JRH; Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Nishizawa T; Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Lee W; RIKEN SPring-8 Center, Sayo-gun, Japan.
  • Park SY; Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Nature ; 606(7916): 1027-1031, 2022 06.
Article en En | MEDLINE | ID: mdl-35580630
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Virales / Ácidos y Sales Biliares / Virus de la Hepatitis B / Microscopía por Crioelectrón / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Virales / Ácidos y Sales Biliares / Virus de la Hepatitis B / Microscopía por Crioelectrón / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Japón
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