Ca²⁺-saturated calmodulin binds tightly to the N-terminal domain of A-type fibroblast growth factor homologous factors.

ABSTRACT: Voltage-gated sodium channels (Na_vs) are tightly regulated by multiple conserved auxiliary proteins, including the four fibroblast growth factor homologous factors (FGFs), which bind the Na_v EF-hand like domain (EFL), and calmodulin (CaM), a multifunctional messenger protein that binds the Na_V IQ motif. The EFL domain and IQ motif are contiguous regions of Na_V cytosolic C-terminal domains (CTD), placing CaM and FGF in close proximity. However, whether the FGFs and CaM act independently, directly associate, or operate through allosteric interactions to regulate channel function is unknown. Titrations monitored by steady-state fluorescence spectroscopy, structural studies with solution NMR, and computational modeling demonstrated for the first time

SUBMITTER: Mahling R 

PROVIDER: S-EPMC8059062 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature