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Repliegue funcional de la proteína de penetración en un virus sin envoltura

Tobias Herrmann^1,2, Raúl Torres³, Eric N Salgado^3,4

¹Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

|January 14, 2021

Resumen

Los rotavirus utilizan la proteína VP4 para crear lesiones en la membrana para entrar en las células. El análisis estructural revela que el VP4 se reorganiza para exponer un

Área de la Ciencia:

Virología
Biología estructural
Biología celular

Sus antecedentes:

Los virus sin envoltura requieren una ruptura de la membrana para entrar en la célula.
La entrada del rotavirus en las células huésped está mediada por la proteína viral VP4.

Objetivo del estudio:

Esclarecer el mecanismo molecular por el cual la proteína VP4 del rotavirus media la penetración en la membrana.
Para determinar las reorganizaciones estructurales de VP4 durante la entrada viral.

Principales métodos:

Se utilizó la criomicroscopia electrónica (crio-EM) para determinar la estructura de VP4 en la superficie del rotavirus.
Se empleó criotomografía electrónica para visualizar las partículas de virus que entran en las células.
Se utilizó un mutante disulfuro de VP4 para estabilizar las conformaciones intermedias.

Principales resultados:

La VP4 activada (VP8* y VP5*) sufre un cambio conformacional de un estado "vertical" a un estado "invertido" en la superficie del virión.
La conformación VP4 "invertida" expone un dominio "pie" enterrado, que interactúa con la membrana celular huésped.
Los datos criotomográficos apoyan el mecanismo propuesto de penetración en la membrana mediada por VP4.

Conclusiones:

El estudio define el mecanismo molecular de penetración en la membrana del rotavirus, iniciado por cambios conformacionales en la VP4.
Los hallazgos sugieren que el mecanismo de acción de VP4 puede compartir similitudes con otras vías de entrada viral.
Esta investigación proporciona información crítica sobre las primeras etapas de la infección por rotavirus.

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