Domain-domain interactions in filamin A (16-23) impose a hierarchy of unfolding forces.
Biophys J
; 104(9): 2022-30, 2013 May 07.
Article
en En
| MEDLINE
| ID: mdl-23663845
ABSTRACT
The quaternary structure of Filamin A (FLNa) 16-23 was recently shown to exhibit multiple domain-domain interactions that lead to a propeller-like construction. Here we present single-molecule force spectroscopy experiments to show a wide variety of mechanical responses of this molecule and compare it with its linear counterpart FLNa 1-8. The compact structure of FLNa 16-23 leads to a broad distribution of rupture forces and end-to-end lengths in the force-extension mode and multiple unraveling timescales in the force-clamp mode. Moreover, a subset of force-extension trajectories reveals a mechanical hierarchy in which the rupture of domain-domain interactions at high forces (>200 pN) liberates the unfolding of individual domains at low forces (â¼100 pN). This mechanism may also explain the order-of-magnitude difference in the rates of the biexponential fits to the distribution of unfolding dwell times under force-clamp. Overall, FLNa 16-23 under a force of 100 pN is more compliant than the linear FLNa 1-8. Because a physiological role of FLNa is to crosslink actin filaments, this range of responses allows it to accommodate a broad spectrum of forces exerted by the cell and its environment.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Dominios y Motivos de Interacción de Proteínas
/
Desplegamiento Proteico
/
Filaminas
Límite:
Animals
Idioma:
En
Año:
2013
Tipo del documento:
Article