Exploring the Activation Mechanism of the mGlu5 Transmembrane Domain.

ABSTRACT: As a class C GPCR and regulator of synaptic activity, mGlu5 is an attractive drug target, potentially offering treatment for several neurologic and psychiatric disorders. As little is known about the activation mechanism of mGlu5 at a structural level, potential of mean force calculations linked to molecular dynamics simulations were performed on the mGlu5 transmembrane domain crystal structure to explore various internal mechanisms responsible for its activation. Our results suggest that the hydrophilic interactions between intracellular loop 1 and the intracellular side of TM6 have to be disrupted to reach a theoretically active-like conformation. In addition, interactions between residues that are key for mGlu5 activation (Tyr659^3.44 and Ile751^5.51) and mGlu5 inact

SUBMITTER: Lans I 

PROVIDER: S-EPMC7069277 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature