The mechanism and energetics of the dynein priming stroke.
Structure
; 32(5): 603-610.e4, 2024 May 02.
Article
em En
| MEDLINE
| ID: mdl-38430911
ABSTRACT
Dyneins are an AAA+ motor responsible for motility and force generation toward the minus end of microtubules. Dynein motility is powered by nucleotide-dependent transitions of its linker domain, which transitions between straight (post-powerstroke) and bent (pre-powerstroke) conformations. To understand the dynamics and energetics of the linker, we performed all-atom molecular dynamics simulations of human dynein-2 primed for its power stroke. Simulations revealed that the linker can adopt either a bent conformation or a semi-bent conformation, separated by a 5.7 kT energy barrier. The linker cannot switch back to its straight conformation in the pre-powerstroke state due to a steric clash with the AAA+ ring. Simulations also showed that an isolated linker has a free energy minimum near the semi-bent conformation in the absence of the AAA+ ring, indicating that the linker stores energy as it bends and releases this energy during the powerstroke.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Dineínas
/
Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article