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Updated: Sep 23, 2025
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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
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Conocimientos estructurales sobre el receptor del VHB y el transportador de ácido biliar NTCP
Jae-Hyun Park1, Masashi Iwamoto2, Ji-Hye Yun3,4
1Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
Nature
|May 17, 2022
Resumen
El virus de la hepatitis B (VHB) utiliza el receptor de polipéptido cotransportador de taurocolato de sodio (NTCP) para infectar las células del hígado. Los científicos resolvieron la estructura de NTCP, revelando un bolsillo único para el desarrollo potencial de fármacos contra el VHB.
Área de la Ciencia:
- Biología estructural
- Virología
- Hepatología
Sus antecedentes:
- El virus de la hepatitis B (VHB) infecta a aproximadamente 250 millones de personas en todo el mundo.
- La coinfección con el virus de la hepatitis D (VHD) aumenta el riesgo de enfermedad hepática grave.
- El polipéptido cotransportador de taurocolato de sodio (NTCP) es el receptor identificado para la entrada del VHB.
Objetivo del estudio:
- Para determinar la estructura tridimensional del transportador NTCP humano.
- Para aclarar la base estructural de la interacción del VHB con el NTCP.
- Para identificar posibles objetivos para el diseño de fármacos antivirales.
Principales métodos:
- Para resolver la estructura del NTCP se empleó la criomicroscopia electrónica (criomioscopía).
- La estructura de NTCP se determinó en complejo con un anticuerpo unido.
- Se realizó un análisis comparativo con proteínas de la familia de portadores de solutos 10 (SLC10).
Principales resultados:
- La estructura cryo-EM de NTCP fue resuelta con éxito.
- El NTCP carece de la primera hélice transmembrana presente en otras proteínas SLC10.
- Se identificó una bolsa única que interactúa con el dominio preS1 del VHB en la cara extracelular del NTCP.
Conclusiones:
- La estructura resuelta de NTCP proporciona información sobre los mecanismos de transporte de ácido biliar.
- La bolsa de interacción preS1 identificada ofrece un nuevo objetivo para el desarrollo de terapias contra el VHB.
- Se pueden explorar estrategias de diseño de fármacos basadas en la estructura para inhibir la entrada del VHB.
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