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Un modelo estructural del complejo BAF humano endógeno informa los mecanismos de la enfermedad

Nazar Mashtalir¹, Hiroshi Suzuki², Daniel P Farrell³

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

|October 14, 2020

Resumen

Los investigadores revelan la estructura del complejo BAF humano unido a los nucleosomas, detallando cómo remodela la cromatina. Esta visión estructural del complejo BAF (factor asociado BRG1/BRM) ayuda a comprender su papel en la salud y la enfermedad.

Área de la Ciencia:

Biología molecular
Biología estructural
La genómica

Sus antecedentes:

Los complejos SWI / SNF de mamíferos son remodeladores cruciales de la cromatina dependientes del ATP.
Estos complejos regulan la arquitectura genómica y la expresión génica.

Objetivo del estudio:

Presentar un modelo estructural del complejo BAF canónico humano unido a un nucleosoma.
Investigar el impacto funcional de las mutaciones asociadas a la enfermedad.

Principales métodos:

Microscopía cryoelectrónica (cryo-EM)
Espectrometría de masas de enlace transversal
Modelado por homología
Ensayos bioquímicos

Principales resultados:

Se generó un modelo estructural del complejo BAF unido al nucleosoma.
Los complejos BAF activan parches nucleosómicos ácidos a través de subunidades específicas (SMARCB1, SMARCA4/2).
Las mutaciones de la enfermedad en estas regiones afectan la remodelación de la cromatina.
Se identificaron mutaciones asociadas al cáncer que afectan a las interfaces BAF.

Conclusiones:

El estudio proporciona información biofísica sobre la función del complejo BAF.
Comprender la estructura del BAF es clave para descifrar su papel en los procesos celulares normales y en enfermedades como el cáncer.

Palabras clave:

Remodelación de la cromatina dependiente del ATP El complejo BAF el cáncer Espectrometría de masas de enlace transversal Microscopía electrónica criogénica Modelado por homología complejos SWI/SNF de mamíferos mutaciones

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