Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM.
Nat Struct Mol Biol
; 25(6): 528-537, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29867215
ABSTRACT
The function of actin is coupled to the nucleotide bound to its active site. ATP hydrolysis is activated during polymerization; a delay between hydrolysis and inorganic phosphate (Pi) release results in a gradient of ATP, ADP-Pi and ADP along actin filaments (F-actin). Actin-binding proteins can recognize F-actin's nucleotide state, using it as a local 'age' tag. The underlying mechanism is complex and poorly understood. Here we report six high-resolution cryo-EM structures of F-actin from rabbit skeletal muscle in different nucleotide states. The structures reveal that actin polymerization repositions the proposed catalytic base, His161, closer to the γ-phosphate. Nucleotide hydrolysis and Pi release modulate the conformational ensemble at the periphery of the filament, thus resulting in open and closed states, which can be sensed by coronin-1B. The drug-like toxin jasplakinolide locks F-actin in an open state. Our results demonstrate in detail how ATP hydrolysis links to F-actin's conformational dynamics and protein interaction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Actinas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article