Papel esencial de las bobinas enrolladas para la agregación y actividad de priones ricos en Q/N y proteínas PolyQ

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Ferdinando Fiumara¹, Luana Fioriti, Eric R Kandel

¹Department of Neuroscience, Columbia University, New York, NY 10032, USA.

|December 25, 2010

Resumen

Los priones ricos en glutamina/asparagina y las proteínas polyQ se agregan a través de bobinas enrolladas alfa-hélices, no sólo hojas beta. La interrupción de las bobinas enrolladas perjudica la función, mientras que su mejora promueve la agregación, revelando un nuevo modelo de enfermedad.

Área de la Ciencia:

La agregación de proteínas agregación de proteínas
Las enfermedades neurodegenerativas son enfermedades neurodegenerativas.
Biología estructural Biología estructural.

Sus antecedentes:

Los priones ricos en glutamina/asparagina (Q/N) y las proteínas poliQ expandidas están implicados en la neurotoxicidad y las enfermedades.
Su agregación a menudo se atribuye a la formación de hojas beta.

Objetivo del estudio:

Investigar el papel de los dominios de bobina en espiral en la agregación de proteínas ricas en Q/N y poliQ.
Explorar la participación de las bobinas en espiral en la conmutación funcional priónica y la patogénesis de la enfermedad poliQ.

Principales métodos:

Análisis bioinformático de los socios de interacción de las proteínas.
Estudios in vitro utilizando dicroísmo circular y enlaces cruzados químicos.
Mutagénesis guiada por la estructura in vivo.

Principales resultados:

Los dominios de bobina enrollada se encontraron recurrentemente en segmentos de proteínas ricas en Q / N y poliQ y sus socios de interacción.
Los péptidos ricos en Q/N y poliQ forman bobinas enrolladas alfa-hélices y multiméricos in vitro.
Mutaciones que afectan a las bobinas enrolladas moduladas in vivo agregación y actividad de priones ricos en Q/N y poliQ-huntingtina expandida.

Conclusiones:

Las bobinas enrolladas juegan un papel crítico en la agregación de proteínas ricas en Q/N y poliQ.
Un modelo de bobina en espiral explica el cambio funcional de priones ricos en Q/N y la patogénesis de enfermedades poliQ.

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