Mechanistic Understanding of the Palmitoylation of G_o Protein in the Allosteric Regulation of Adhesion Receptor GPR97.

ABSTRACT: Adhesion G-protein-coupled receptors (aGPCRs)-a major family of GPCRs-play critical roles in the regulation of tissue development and cancer progression. The orphan receptor GPR97, activated by glucocorticoid stress hormones, is a prototypical aGPCR. Although it has been established that the palmitoylation of the C-terminal G_o protein is essential for G_o's efficient engagement with the active GPR97, the detailed allosteric mechanism remains to be clarified. Hence, we performed extensive large-scale molecular dynamics (MD) simulations of the GPR97-G_o complex in the presence or absence of G_o palmitoylation. The conformational landscapes analyzed by Markov state models revealed that the overall conformation of GPR97 is preferred to be fully active w

SUBMITTER: Zhang H 

PROVIDER: S-EPMC9504338 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature