Periphery Pre-S1 and S1 helix nexus for PIP2 at TRPC3 channel.
Cell Calcium
; 123: 102932, 2024 Nov.
Article
em En
| MEDLINE
| ID: mdl-39094223
ABSTRACT
Transient receptor potential canonical 3 (TRPC3) is a calcium-permeable, non-selective cation channel known to be regulated by components of the phospholipase C (PLC)-mediated signaling pathway, such as Ca2+, diacylglycerol (DAG) and phosphatidylinositol 4,5-biphosphate (PI(4,5)P2). However, the molecular gating mechanism by these regulators is not yet fully understood, especially its regulation by PI(4,5)P2, despite the importance of this channel in cardiovascular pathophysiology. Recently, Clarke et al. (2024) have reported that PI(4,5)P2 is a positive modulator for TRPC3 using molecular dynamics simulations and patch-clamp techniques. They have demonstrated a multistep gating mechanism of TRPC3 with the binding of PI(4,5)P2 to the lipid binding site located at the pre-S1/S1 nexus, and the propagation of PI(4,5)P2 sensing to the pore domain via a salt bridge between the TRP helix and the S4-S5 linker.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 4,5-Difosfato
/
Canais de Cátion TRPC
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article