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Estructura de la holoenzima de la ADN polimerasa del virus de la viruela del mono

Qi Peng¹, Yufeng Xie², Lu Kuai¹

¹CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Science (New York, N.Y.)

|December 15, 2022

Resumen

La replicación del ADN del virus Mpox se aclaró mediante la determinación de la estructura de su holoenzima polimerasa. Este hallazgo revela un mecanismo de "enganche de deslizamiento hacia adelante" y puede ayudar a desarrollar nuevos medicamentos antivirales.

Área de la Ciencia:

Virología
Biología estructural
Descubrimiento de drogas

Sus antecedentes:

La Mpox (varicela de monos) fue declarada una emergencia de salud global en julio de 2022, destacando la necesidad urgente de tratamientos.
El virus mpox (MPXV) se basa en su ADN polimerasa (F8) y cofactores (A22, E4) para la replicación del genoma.

Objetivo del estudio:

Para determinar la estructura de la holoenzima polimerasa de ADN MPXV unida al ADN.
Para aclarar el mecanismo de la replicación del genoma viral.

Principales métodos:

Se utilizó la microscopía criolectrónica para determinar la estructura de la holoenzima a una resolución de ~2.8 angstroms.
El análisis estructural se centró en la unión al ADN y la arquitectura de la polimerasa.

Principales resultados:

La estructura de la holoenzima revela un mecanismo de "clampe de deslizamiento hacia adelante" para la replicación procesal del ADN.
La polimerasa MPXV exhibe un modo de unión al ADN conservado entre las polimerasas de la familia B.

Conclusiones:

El estudio aclara el mecanismo de replicación del genoma MPXV.
Los hallazgos proporcionan una base estructural para el desarrollo de nuevas terapias contra el virus de la viruela.

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