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La estructura del complejo MIND define un enfoque regulatorio para el ensamblaje de cinetocoros de levadura
Yoana N Dimitrova1, Simon Jenni1, Roberto Valverde1
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Cell
|November 25, 2016
Resumen
El complejo MIND conecta los centrómeros con los microtúbulos. Su estructura revela cómo la fosforilación de Dsn1 regula el ensamblaje de cinetocoros mediante el control de las interacciones con Mif2, COMA y el complejo Ndc80.
Área de la Ciencia:
- Biología celular
- Biología estructural
- Biología molecular
Sus antecedentes:
- Los cinetocoros son estructuras proteicas cruciales que conectan el ADN centromérico con los microtúbulos del huso durante la división celular.
- El complejo MIND (Mtw1, Nnf1, Nsl1, Dsn1) es un componente clave del cinetocoro, análogo al complejo metazoario Mis12.
- MIND conecta los elementos centromero-proximales (Mif2, COMA) con el complejo de unión de microtúbulos Ndc80.
Objetivo del estudio:
- Para determinar la estructura cristalina del complejo Kluyveromyces lactis MIND.
- Aclarar los mecanismos moleculares subyacentes al papel de MIND en el ensamblaje de cinetocoros y la fijación de microtúbulos.
- Comprender cómo MIND integra las señales reguladoras para la formación dinámica de cinetocoros.
Principales métodos:
- Cristalografía de rayos X para obtener la estructura de alta resolución del complejo MIND de Kluyveromyces lactis.
- Ensayos bioquímicos para analizar las interacciones proteína-proteína y los mecanismos reguladores.
- Análisis basado en la estructura de dominios conservados e interfaces de interacción.
Principales resultados:
- El complejo MIND adopta una estructura alargada y asimétrica en forma de Y con dos cabezas globulares y un eje en espiral.
- Una extensión N-terminal de Dsn1 actúa como un dominio autoinhibidor, bloqueando la unión de Mif2/COMA.
- La fosforilación de Dsn1 por Ipl1/Aurora B quinasa alivia la autoinhibición, lo que facilita el ensamblaje de las cinetocoras.
- Una extensión del terminal C Dsn1 sirve como sitio de acoplamiento para el complejo Ndc80.
Conclusiones:
- La estructura compleja de MIND revela un mecanismo sofisticado para regular el ensamblaje de cinetocoros a través de la autoinhibición y la regulación de fosfo.
- Dsn1 juega un papel central en la integración de los componentes centroméricos y de unión de microtúbulos del cinetocoro.
- Este estudio proporciona información a nivel atómico sobre el proceso dinámico de formación de cinetocoros y la fijación de microtúbulos.
Palabras clave:
CENP-C, por sus siglas en inglésEl complejo Ctf19Ipl1/AuroraB regulación del fósforoMif2 y sus derivadosNo es cierto.El complejo Ndc80división celularEstructura de las cinetocorasLevadura de punto-centromeroCristalografía de rayos XMás Videos Relacionados
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