Lis1 relieves cytoplasmic dynein-1 autoinhibition by acting as a molecular wedge.
Nat Struct Mol Biol
; 30(9): 1357-1364, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37620585
ABSTRACT
Cytoplasmic dynein-1 transports intracellular cargo towards microtubule minus ends. Dynein is autoinhibited and undergoes conformational changes to form an active complex that consists of one or two dynein dimers, the dynactin complex, and activating adapter(s). The Lissencephaly 1 gene, LIS1, is genetically linked to the dynein pathway from fungi to mammals and is mutated in people with the neurodevelopmental disease lissencephaly. Lis1 is required for active dynein complexes to form, but how it enables this is unclear. Here, we present a structure of two yeast dynein motor domains with two Lis1 dimers wedged in-between. The contact sites between dynein and Lis1 in this structure, termed 'Chi,' are required for Lis1's regulation of dynein in Saccharomyces cerevisiae in vivo and the formation of active human dynein-dynactin-activating adapter complexes in vitro. We propose that this structure represents an intermediate in dynein's activation pathway, revealing how Lis1 relieves dynein's autoinhibited state.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lisencefalias Clásicas y Heterotopias Subcorticales en Banda
/
Dineínas Citoplasmáticas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos