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Análisis estructural del mecanismo de unión del adenovirus a su receptor celular humano, CAR
M C Bewley1, K Springer, Y B Zhang
1Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Science (New York, N.Y.)
|November 24, 1999
Resumen
La estructura cristalina revela cómo el botón de fibra de adenovirus se une al coxsackie y al receptor de adenovirus (CAR), identificando objetivos potenciales para medicamentos antivirales y modificación de vectores de terapia génica.
Área de la Ciencia:
- Biología estructural Biología estructural.
- Virología Virología.
- Interacciones moleculares Las interacciones moleculares.
Sus antecedentes:
- La unión del virus con la célula huésped es crucial para la infección, pero se entiende mal.
- El adenovirus utiliza su dominio de fibra para unirse a las células huésped.
Objetivo del estudio:
- Determinar la base molecular de la fibra del adenovirus que se une a su receptor humano, CAR.
- Identificar objetivos potenciales para terapias antivirales y el desarrollo de vectores de terapia génica.
Principales métodos:
- Se utilizó la cristalografía de rayos X para obtener la estructura del dominio del botón de fibra del adenovirus en complejo con el dominio CAR I.
Principales resultados:
- La estructura cristalina revela una unión de alta afinidad mediada por bucles expuestos a la superficie en la perilla que entra en contacto con CAR.
- Los desajustes de topología crean cavidades y canales en la interfaz, lo que sugiere posibles blancos de drogas.
- Se identificaron los determinantes clave de la especificidad vinculante.
Conclusiones:
- La estructura determinada proporciona una visión crítica de las interacciones adenovirus-CAR.
- Los hallazgos pueden guiar el desarrollo de nuevas estrategias antivirales y la ingeniería de vectores de terapia génica de adenovirus con tropismo alterado.
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