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Bases estructurales para el reconocimiento selectivo de oligosacáridos por DC-SIGN y DC-SIGNR
H Feinberg1, D A Mitchell, K Drickamer
1Department of Structural Biology, University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|December 12, 2001
Resumen
La molécula de adhesión intracelular específica de las células dendríticas-3 agarrando la nonintegrina (DC-SIGN) se une al VIH, promoviendo la infección. Comprender la unión de DC-SIGN y DC-SIGNR a los oligosacáridos con alto contenido de manosa puede conducir a nuevos fármacos profilácticos contra el VIH.
Área de la Ciencia:
- Inmunología Inmunología.
- Virología Virología.
- Biología Estructural Biología estructural.
Sus antecedentes:
- La no integrina agarradora de la molécula de adhesión intracelular específica de células dendríticas-3 (DC-SIGN) es una lectina de tipo C en las células dendríticas que se une a ICAM-3, mediando las interacciones iniciales de las células T.
- DC-SIGN y el receptor DC-SIGNR relacionado se unen a los oligosacáridos en la envoltura del virus de la inmunodeficiencia humana (VIH), lo que mejora la infección viral de las células T.
Objetivo del estudio:
- Para aclarar la base estructural de DC-SIGN y DC-SIGNR reconocimiento de oligosacáridos.
- Explorar el potencial de estas interacciones para el desarrollo de nuevos fármacos profilácticos contra el VIH.
Principales métodos:
- Se utilizó cristalografía de rayos X para determinar las estructuras de los dominios de reconocimiento de carbohidratos de DC-SIGN y DC-SIGNR unidos a oligosacáridos.
- Se llevaron a cabo estudios vinculantes para evaluar la selectividad de estos receptores para oligosacáridos específicos.
Principales resultados:
- Las estructuras cristalinas revelaron cómo DC-SIGN y DC-SIGNR se unen a estructuras específicas de oligosacáridos.
- Los estudios vinculantes confirmaron que estos receptores reconocen selectivamente los oligosacáridos endógenos de alta manosa.
Conclusiones:
- El reconocimiento selectivo de los oligosacáridos altos en manosa por DC-SIGN y DC-SIGNR proporciona una comprensión molecular de su papel en la infección por VIH.
- Dirigirse a estas interacciones representa una nueva estrategia prometedora para desarrollar una profilaxis efectiva del VIH.
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