Fine-Tuning of the Neuropeptide Y1 G Protein-Coupled Receptor by the Tryptophan^6.48 "Toggle Switch".

ABSTRACT: G protein-coupled receptors (GPCRs) transduce extracellular signals into the cell through binding and activation of intracellular effector proteins. Highly conserved residues such as tryptophan W^6.48 of transmembrane helix 6 can play a role in GPCR activation, where W^6.48 acts as a microswitch, changing its rotameric state depending on whether the receptor is bound to an agonist or antagonist. However, its exact role is not entirely clear. Here we investigate the role of W^6.48 in the neuropeptide Y1 receptor (Y1R). Via NMR experiment and molecular dynamics simulations, we find that on the one hand, W^6.48 exhibits multiple rotameric conformations, where simulations indicate that these are coupled to backbone structure. On the other hand, mutation

SUBMITTER: Voitel M 

PROVIDER: S-EPMC12814323 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature