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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
La red de proteínas del VIH en ciernes
Uta K von Schwedler1, Melissa Stuchell, Barbara Müller
1Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA.
Cell
|September 25, 2003
Resumen
La liberación viral, incluido el VIH, depende de las proteínas celulares que forman cuerpos multivesiculares (MVB). Una red de proteínas humanas de clase E, cruciales para la biogénesis de MVB, es esencial para el brote y la liberación de partículas de VIH.
Área de la Ciencia:
- Biología celular Biología celular.
- Virología Virología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La liberación del virus de la inmunodeficiencia humana (VIH) depende de la proteína celular TSG101.
- TSG101 clasifica las proteínas en cuerpos multivesiculares (MVB), que están involucrados en el brote del VIH.
- El papel de otras proteínas involucradas en la biogénesis de MVB en la liberación del VIH sigue sin estar claro.
Objetivo del estudio:
- Investigar si otras proteínas humanas de clase E, involucradas en la biogénesis de MVB, participan en la liberación del VIH.
- Para dilucidar la red de interacción proteína-proteína de las proteínas humanas de clase E.
- Para determinar la participación directa de estas proteínas en el proceso de brote viral.
Principales métodos:
- Identificación de 22 proteínas humanas candidatas de la clase E.
- Análisis de las interacciones proteína-proteína para mapear la red.
- Prueba de la unión de proteínas específicas a las proteínas Gag virales.
- Expresión de mutantes dominantes negativos para evaluar el impacto en el brote del VIH.
Principales resultados:
- Se identificó una red coherente de 22 proteínas humanas de clase E, vinculadas por 43 interacciones.
- Se descubrió que AIP1 es un enlace clave entre los complejos de vías tempranas (TSG101/ESCRT-I) y tardías (CHMP4/ESCRT-III).
- AIP1 se une directamente a las proteínas p6 ((Gag) y EIAV p9 ((Gag) del VIH-1.
- Se detectaron proteínas humanas de clase E en las partículas de VIH-1.
- Los mutantes negativos dominantes de las proteínas de acción tardía de la clase E inhibieron el brote del VIH-1.
Conclusiones:
- Se ha definido una red de proteínas esencial para la biogénesis humana de MVB.
- Toda esta red participa en la liberación del VIH.
- Los hallazgos sugieren que esta red de biogénesis MVB está probablemente involucrada en la liberación de muchos otros virus.
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