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La P5A-ATPasa del retículo endoplasmático es una dislocación de la hélice transmembrana
Michael J McKenna1, Sue Im Sim2, Alban Ordureau1
1Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|September 25, 2020
Resumen
El transportador P5A-ATPasa Spf1 extrae las proteínas transmembrana mal dirigidas del retículo endoplasmático. Este descubrimiento revela un nuevo mecanismo para corregir los errores de orientación de proteínas.
Área de la Ciencia:
- Biología celular
- Biología molecular
- La bioquímica
Sus antecedentes:
- La identidad de las organelas se basa en la composición precisa de las proteínas.
- Los mecanismos para eliminar las proteínas mal dirigidas de los orgánulos no se comprenden completamente.
Objetivo del estudio:
- Investigar el papel del transportador ATP13A1 (Spf1) de la P5A-adenosina trifosfatasa (ATPasa) en el control de la calidad de las proteínas.
- Para aclarar cómo las proteínas mal dirigidas se reconocen y se eliminan del retículo endoplasmático (ER).
Principales métodos:
- Se utilizó la criomicroscopia electrónica para determinar la estructura de Saccharomyces cerevisiae Spf1.
- Investigó la interacción entre Spf1 y los segmentos transmembrana de las proteínas ancladas en la cola.
- Actividad evaluada de la P5A-ATPasa en la extracción de proteínas de la ER.
Principales resultados:
- Spf1 interactúa directamente con los segmentos transmembranares de las proteínas ancladas en la cola.
- La actividad de la P5A-ATPasa facilita la extracción de proteínas mal dirigidas de la ER.
- El análisis estructural reveló una bolsa de unión al sustrato capaz de unir segmentos de transmembrana alfa-hélica.
Conclusiones:
- La P5A-ATPasa puede dislocar las hélices hidrofóbicas mal insertadas de la ER.
- Esta dislocación TM por P5A-ATPasa representa una nueva clase de sustratos de la ATPasa tipo P.
- Este mecanismo puede corregir errores en la orientación de las proteínas y la topogénesis.
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