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La estructura de la proteasa AAA+ de la membrana interna mitocondrial YME1 da una idea del procesamiento del sustrato

Cristina Puchades^1,2, Anthony J Rampello³, Mia Shin^1,2

¹Department of Integrative Structural and Computational Biology, The Scripps Research Institute HZ 175, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|November 4, 2017

Resumen

Revelamos la estructura atómica de la levadura YME1, una proteasa AAA+ mitocondrial interna. Esta estructura muestra cómo las ATPasas se involucran y translocan sustratos de proteínas desplegados a través de un mecanismo de escalera de caracol para el control de calidad.

Área de la Ciencia:

Biología molecular
Biología estructural
Control de calidad celular

Sus antecedentes:

Las proteasas AAA+ son cruciales para mantener la proteostasis celular.
YME1 es una proteasa esencial de la membrana mitocondrial interna AAA+ involucrada en el control de calidad.
Comprender el mecanismo de la translocación del sustrato es clave para comprender la función de la proteasa.

Objetivo del estudio:

Para determinar la estructura atómica de la proteasa YME1 de la levadura unida al sustrato.
Para aclarar el mecanismo de compromiso del sustrato y la translocación por AAA+ ATPases.
Proporcionar información sobre el mecanismo de translocación conservado de las proteínas AAA+.

Principales métodos:

Microscopía cryoelectrónica (cryo-EM) con una resolución de hasta 3,4 angstroms.
Construcción del modelo atómico de la proteasa YME1 de la levadura.
Análisis de los estados de unión de nucleótidos y su efecto sobre la interacción del sustrato.

Principales resultados:

Se obtuvo una estructura crio-EM de ~3,4 angstroms de la levadura ligada al sustrato YME1.
La estructura revela ATPasas AAA + que forman una escalera en espiral alrededor de un sustrato desplegado.
Los estados de nucleótidos distintos controlan alostericamente el compromiso y la translocación del sustrato a través del posicionamiento de la tirosina.

Conclusiones:

Un ciclo secuencial de hidrólisis de ATP alrededor del anillo impulsa la translocación gradual del sustrato.
Un enlazador tipo bisagra acomoda movimientos a gran escala entre la espiral de ATPasa y la base proteolítica.
Es probable que el mecanismo de translocación elucidado se conserve en varias ATPasas AAA+.

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