Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex.

ABSTRACT: Smoothened (SMO) is an oncoprotein and signal transducer in the Hedgehog signaling pathway that regulates cellular differentiation and embryogenesis. As a member of the Frizzled (Class F) family of G protein-coupled receptors (GPCRs), SMO biochemically and functionally interacts with Gi family proteins. However, key molecular features of fully activated, G protein-coupled SMO remain elusive. We present the atomistic structure of activated human SMO complexed with the heterotrimeric Gi protein and two sterol ligands, equilibrated at 310 K in a full lipid bilayer at physiological salt concentration and pH. In contrast to previous experimental structures, our equilibrated SMO complex exhibits complete breaking of the pi-cation interaction between R451^6.32 and W535^7.55, a

SUBMITTER: Vo AP 

PROVIDER: S-EPMC10710022 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature