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In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Bases estructurales para la escisión específica de las cadenas de poliubiquitina ligadas a Lys 63
Yusuke Sato1, Azusa Yoshikawa, Atsushi Yamagata
1Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
Nature
|September 2, 2008
Resumen
El estudio revela la estructura de AMSH-LP, una enzima deubiquitinante (DUB), compleja con una cadena específica de ubiquitina. Esta estructura aclara cómo AMSH-LP elimina las cadenas de poliubiquitina ligadas a Lys 63, cruciales para el tráfico de receptores.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las enzimas desubiquitinantes (DUB) son reguladores críticos de los procesos celulares mediante la eliminación de la ubiquitina.
- AMSH y AMSH-LP son DUB dependientes de zinc que participan en el tráfico de receptores a través de la escisión de la cadena de poliubiquitina ligada a Lys 63.
Objetivo del estudio:
- Para determinar las estructuras cristalinas del dominio humano AMSH-LP DUB.
- Para dilucidar el mecanismo de la deubiquitinación específica del enlace de Lys 63 por miembros de la familia AMSH.
Principales métodos:
- Se utilizó cristalografía de rayos X para obtener estructuras del dominio AMSH-LP DUB solo y en complejo con di-ubiquitina ligada a Lys 63.
- Se realizó un análisis estructural de alta resolución (1.2 A y 1.6 A).
Principales resultados:
- La estructura cristalina del dominio AMSH-LP DUB revela un núcleo catalítico con dos inserciones (Ins-1 e Ins-2).
- La estructura muestra interacciones específicas entre la enzima y las moléculas de ubiquitina tanto distales como proximales en la cadena ligada de Lys 63.
- Se identificó una ranura catalítica que acomoda los principales residuos de ubiquitina y el enlace isopéptido.
Conclusiones:
- Esta es la primera estructura reportada de un DUB complejo con una cadena de ubiquitina ligada a un isopéptido.
- Los hallazgos revelan el mecanismo molecular subyacente a la deubiquitinación específica del enlace de Lys 63 por parte de los DUB de la familia AMSH.
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