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Inserción gradual e inversión de una secuencia de anclaje de señal de tipo II en el complejo ribosoma-Sec61
Prasanna K Devaraneni1, Brian Conti, Yoshihiro Matsumura
1Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97239, USA.
Cell
|July 7, 2011
Resumen
El complejo translocónico ribosoma-Sec61 (RTC) controla con precisión la topología de las proteínas de la membrana. Guía a los anclajes de señal a través de cuatro pasos distintos, incluido un mecanismo de inversión único para la topología de tipo II.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Biogénesis de proteínas de membrana Biogénesis de proteínas de membrana.
Sus antecedentes:
- El complejo ribosoma-Sec61 translocon (RTC) es crucial para la inserción de proteínas de membrana y la topología en las células eucariotas.
- Comprender cómo los anclajes de señal logran su orientación correcta es vital para la biogénesis de las proteínas.
Objetivo del estudio:
- Para aclarar el mecanismo paso a paso por el cual un ancla de señal de tipo II (SA) adquiere su topología de membrana.
- Investigar el papel del RTC en la coordinación de la topogénesis SA.
Principales métodos:
- Utilizó ensayos de fotocrosslinking, apagado por colisión, accesibilidad a la cisteína y protección por proteasa.
- Analizó la topología de un SA canónico de tipo II durante su interacción con el RTC.
Principales resultados:
- Identificó cuatro pasos distintos y estrechamente acoplados en la topogénesis SA tipo II: inserción cabeza-primero, acumulación de cadena, inversión de topología y translocación terminal C.
- Demostró que la progresión de la longitud de la cadena induce distintos cambios en el entorno molecular y transiciones energéticas.
- Se reveló que la inversión SA tipo II ocurre en un intermedio inestable regulado por las interacciones ribosoma-translocon.
Conclusiones:
- El RTC orquesta la topogénesis del anclaje de la señal a través de un proceso secuencial y controlado energéticamente dentro de un entorno protegido.
- Las interacciones dinámicas ribosoma-translocon son críticas para regular el paso de inversión en la adquisición de la topología SA tipo II.
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