Residue 6.43 defines receptor function in class F GPCRs.

ABSTRACT: The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD_1-10) subtypes and Smoothened (SMO), remains one of the most enigmatic GPCR families. While SMO relies on cholesterol binding to the 7TM core of the receptor to activate downstream signaling, underlying details of receptor activation remain obscure for FZDs. Here, we aimed to investigate the activation mechanisms of class F receptors utilizing a computational biology approach and mutational analysis of receptor function in combination with ligand binding and downstream signaling assays in living cells. Our results indicate that FZDs differ substantially from SMO in receptor activation-associated conformational changes. SMO manifests a preference for a straight TM6 in both ligand binding and

SUBMITTER: Turku A 

PROVIDER: S-EPMC8225760 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature