Exploring the constitutive activation mechanism of the class A orphan GPR20.

ABSTRACT: GPR20, an orphan G protein-coupled receptor (GPCR), shows significant expression in intestinal tissue and represents a potential therapeutic target to treat gastrointestinal stromal tumors. GPR20 performs high constitutive activity when coupling with G_i. Despite the pharmacological importance of GPCR constitutive activation, determining the mechanism has long remained unclear. In this study, we explored the constitutive activation mechanism of GPR20 through large-scale unbiased molecular dynamics simulations. Our results unveil the allosteric nature of constitutively activated GPCR signal transduction involving extracellular and intracellular domains. Moreover, the constitutively active state of the GPR20 requires both the N-terminal cap and G_i protein. The N-terminal

SUBMITTER: Zhang MY 

PROVIDER: S-EPMC11747167 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature