Molecular basis of outer kinetochore assembly on CENP-T.
Elife
; 52016 12 24.
Article
em En
| MEDLINE
| ID: mdl-28012276
ABSTRACT
Stable kinetochore-microtubule attachment is essential for cell division. It requires recruitment of outer kinetochore microtubule binders by centromere proteins C and T (CENP-C and CENP-T). To study the molecular requirements of kinetochore formation, we reconstituted the binding of the MIS12 and NDC80 outer kinetochore subcomplexes to CENP-C and CENP-T. Whereas CENP-C recruits a single MIS12NDC80 complex, we show here that CENP-T binds one MIS12NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1Cyclin B complex at three distinct CENP-T sites. Visualization of reconstituted complexes by electron microscopy supports this model. Binding of CENP-C and CENP-T to MIS12 is competitive, and therefore CENP-C and CENP-T act in parallel to recruit two MIS12 and up to four NDC80 complexes. Our observations provide a molecular explanation for the stoichiometry of kinetochore components and its cell cycle regulation, and highlight how outer kinetochore modules bridge distances of well over 100 nm.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteínas Cromossômicas não Histona
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Cinetocoros
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Multimerização Proteica
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Proteínas Associadas aos Microtúbulos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article