Exploring the activation mechanism of metabotropic glutamate receptor 2.

ABSTRACT: Homomeric dimerization of metabotropic glutamate receptors (mGlus) is essential for the modulation of their functions and represents a promising avenue for the development of novel therapeutic approaches to address central nervous system diseases. Yet, the scarcity of detailed molecular and energetic data on mGlu2 impedes our in-depth comprehension of their activation process. Here, we employ computational simulation methods to elucidate the activation process and key events associated with the mGlu2, including a detailed analysis of its conformational transitions, the binding of agonists, G_i protein coupling, and the guanosine diphosphate (GDP) release. Our results demonstrate that the activation of mGlu2 is a stepwise process and several energy barriers need to be overcome. Mo

SUBMITTER: Zhu X 

PROVIDER: S-EPMC11126994 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature