Modeling of full-length Piezo1 suggests importance of the proximal N-terminus for dome structure.
Biophys J
; 120(8): 1343-1356, 2021 04 20.
Article
em En
| MEDLINE
| ID: mdl-33582137
ABSTRACT
Piezo1 forms a mechanically activated calcium-permeable nonselective cation channel that is functionally important in many cell types. Structural data exist for C-terminal regions, but we lack information about N-terminal regions and how the entire channel interacts with the lipid bilayer. Here, we use computational approaches to predict the three-dimensional structure of the full-length Piezo1 and simulate it in an asymmetric membrane. A number of novel insights are suggested by the model 1) Piezo1 creates a trilobed dome in the membrane that extends beyond the radius of the protein, 2) Piezo1 changes the lipid environment in its vicinity via preferential interactions with cholesterol and phosphatidylinositol 4,5-bisphosphate (PIP2) molecules, and 3) cholesterol changes the depth of the dome and PIP2 binding preference. In vitro alteration of cholesterol concentration inhibits Piezo1 activity in a manner complementing some of our computational findings. The data suggest the importance of N-terminal regions of Piezo1 for dome structure and membrane cholesterol and PIP2 interactions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais Iônicos
/
Bicamadas Lipídicas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido