Lis1 Has Two Opposing Modes of Regulating Cytoplasmic Dynein.
Cell
; 170(6): 1197-1208.e12, 2017 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-28886386
ABSTRACT
Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule. We show that these opposing modes depend on the stoichiometry of Lis1 binding to dynein and that this stoichiometry is regulated by the nucleotide state of dynein's AAA3 domain. The low-affinity state requires Lis1 to also bind to dynein at a novel conserved site, mutation of which disrupts Lis1's function in vivo. We propose a new model for the regulation of dynein by Lis1.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Dineínas
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Proteínas de Saccharomyces cerevisiae
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1-Alquil-2-acetilglicerofosfocolina Esterase
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Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos