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Determinante extracitoplasmático no hidrofóbico de la transferencia de parada en la proteína priónica
C S Yost1, C D Lopez, S B Prusiner
1Department of Anesthesia, University of California, San Francisco 94143.
Nature
|February 15, 1990
Resumen
Los investigadores descubrieron que las secuencias extracitoplasmáticas cargadas en la proteína priónica son cruciales para su integración transmembrana y para detener la transferencia. Este hallazgo revela un nuevo mecanismo en la biogénesis de proteínas de membrana.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Bioquímica de las proteínas Bioquímica de las proteínas
- Biología celular Biología celular.
Sus antecedentes:
- Las proteínas transmembranales integrales poseen universalmente dominios hidrofóbicos para la extensión de la membrana y la terminación de la translocación.
- El papel de las secuencias extracitoplasmáticas en la transferencia de parada de proteínas y la integración transmembrana no se ha establecido previamente.
- La proteína priónica exhibe transferencia de parada inusual y topologías alternativas, lo que sugiere secuencias topogénicas únicas.
Objetivo del estudio:
- Investigar los determinantes dentro de la secuencia topogénica de la proteína priónica que gobiernan la topología transmembrana.
- Para aclarar el papel de las secuencias extracitoplasmáticas en el proceso de transferencia de parada.
- Comprender el mecanismo de la biogénesis de las proteínas de membrana.
Principales métodos:
- Utilizamos sistemas de traducción libre de células (germen de trigo y lisado de reticulocitos de conejo) para estudiar la translocación de proteínas.
- Investigó la función de dominios específicos dentro de la secuencia topogénica de la proteína priónica.
- Proteínas heterólogas diseñadas para evaluar las propiedades topogénicas de las secuencias de proteínas priónicas.
Principales resultados:
- Un dominio cargado de disposición luminosa es esencial para detener la transferencia mediada por un dominio hidrofóbico adyacente.
- La disposición espacial entre los dominios cargados e hidrofóbicos es fundamental para una transferencia de parada eficiente.
- Un dominio hidrófilo extracitoplasmático de la proteína priónica confería una topología transmembrana a una proteína heteróloga.
Conclusiones:
- Se identificó un dominio extracitoplasmático funcional inesperado en la proteína priónica que influye en la detención de la transferencia.
- Demostró que las secuencias extracitoplasmáticas cargadas juegan un papel importante en la dirección de la topología de las proteínas.
- Estos hallazgos tienen implicaciones para la comprensión de los mecanismos fundamentales de la biogénesis e integración de las proteínas de membrana.
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