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La ligasa UFM1 E3 promueve el reciclaje de las subunidades ribosómicas 60S de la ER
Paul A DaRosa1, Ivan Penchev2, Samantha C Gumbin1
1Department of Biology, Stanford University, Stanford, CA, USA.
Nature
|February 21, 2024
Resumen
La ubiquitina y las proteínas similares a la ubiquitina (UBL) regulan el comportamiento celular. Este estudio revela cómo la ligasa UFM1 modifica la proteína ribosómica uL24, ayudando al rescate y reciclaje de la subunidad 60S de la membrana ER.
Área de la Ciencia:
- Biología molecular
- Biología celular
- Biología estructural
Sus antecedentes:
- La ubiquitina y las proteínas similares a la ubiquitina (UBL) median procesos celulares cruciales mediante la modificación reversible de las proteínas.
- UFM1 modifica principalmente la proteína ribosómica uL24 en los ribosomas asociados a ER, ayudando al rescate de la subunidad 60S.
- El mecanismo preciso de la selección de objetivos de UFM1 y su papel en el rescate de 60S seguía siendo incierto.
Objetivo del estudio:
- Para aclarar el mecanismo molecular de la UFMilación del ribosoma por la UFM1 E3 ligasa (E3(UFM1).
- Determinar la base estructural para el reconocimiento del sustrato E3 ((UFM1) y la transferencia de UFM1 a uL24.
- Investigar el papel de E3 ((UFM1) en la liberación y el reciclaje de subunidades ribosómicas grandes después de la terminación.
Principales métodos:
- Microscopía cryoelectrónica (cryo-EM) para capturar instantáneas secuenciales de E3 ((UFM1) interactuando con su sustrato.
- Análisis bioquímicos para evaluar la función y las interacciones del mecanismo de UFMilación.
- Estudios in vivo para observar la UFMilación de ribosomas en subunidades libres de 60S.
Principales resultados:
- La UFMilación del ribosoma ocurre en las subunidades libres de 60S in vivo.
- Las estructuras cryo-EM revelan E3 ((UFM1) que se une al tallo L1 y los sitios de unión al tRNA, modificando uL24 a más de 150 Å de distancia.
- E3 ((UFM1) forma una abrazadera estable en forma de C alrededor de la subunidad UFMylated 60S después de la catálisis.
Conclusiones:
- E3 ((UFM1) emplea un mecanismo único para lograr una modificación precisa de uL24 en la subunidad 60S.
- El complejo E3 ((UFM1)-UFMylated 60S probablemente facilita la liberación y el reciclaje de la subunidad ribosómica grande de la membrana ER.
- Este estudio proporciona información estructural sobre el control de la calidad de los ribosomas y la regulación de la síntesis de proteínas en el ER.
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