A molecular trajectory of α-actinin activation.
Biophys J
; 103(10): 2050-9, 2012 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-23200039
ABSTRACT
The mechanisms by which living cells respond to mechanical stimuli are not yet fully understood. It has been suggested that mechanosensing proteins play an important role in mechanotransduction because their binding affinities are directly affected by the external stress. α-Actinin is an actin cross-linker and may act as a mechanosensor in adhesion sites. Its interaction with vinculin is suggested to be mechanically regulated. In this study, the free energy of activation is explored using the umbrella sampling method. An activation trajectory is generated in which α-actinin's vinculin-binding site swings out of the rod domain, leading to approximately an 8 kcal/mol free energy release. The activation trajectory reveals several local and global conformational changes along the activation pathway accompanied by the breakage of a number of key interactions stabilizing the inhibited structure. These results may shed light on the role of α-actinin in cellular mechanotransduction and focal adhesion formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Actinina
/
Modelos Moleculares
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos