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Bases estructurales de la inhibición de la señalización de BMP por la proteína del nudo cistino Noggin Noggin
Jay Groppe1, Jason Greenwald, Ezra Wiater
1Structural Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|December 13, 2002
Resumen
Las proteínas morfogenéticas óseas (BMP) y sus antagonistas, como Noggin, regulan procesos cruciales del desarrollo. Este estudio revela el Noggin Noggin.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología del desarrollo Biología del desarrollo.
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las proteínas morfogenéticas óseas (BMP) y los antagonistas controlan diversos procesos de desarrollo.
- Las estructuras tridimensionales y los mecanismos de inactivación de los antagonistas de BMP eran previamente desconocidos.
Objetivo del estudio:
- Para determinar la estructura tridimensional del antagonista del BMP Noggin unido al BMP-7.
- Para aclarar la base estructural de la inhibición de la señalización de BMP por Noggin.
Principales métodos:
- Cristalografía de rayos X para determinar la estructura de Noggin unido al BMP-7.
- Mutagénesis específica del sitio de Noggin.
- Análisis de la formación ósea y la apoptosis en el desarrollo de las extremidades de los pollitos.
Principales resultados:
- Se determinó la estructura cristalina de Noggin unido al BMP-7.
- Noggin inhibe la señalización de BMP mediante el bloqueo de las interfaces de unión al receptor.
- Las variantes Noggin mostraron una afinidad de unión BMP-7 alterada correlacionada con efectos en el desarrollo.
- Noggin funciona mediante el secuestro de BMP-7 en un complejo inactivo.
Conclusiones:
- Noggin inhibe la señalización de BMP mediante el bloqueo físico de los sitios de interacción del receptor.
- Noggin y BMP comparten un andamio de nudo de cistina similar, lo que sugiere un origen evolutivo común.
- Comprender las interacciones Noggin-BMP proporciona información sobre la regulación del desarrollo.
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