Updated project metadata.
Project employ Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS), to characterise the structural dynamics of turkey β1-adrenergic receptor (tβ1AR) in complex with nine ligands, including agonists, partial agonists and antagonists.We show that dynamic signatures across the GPCR structure can be grouped by compound modality. Surprisingly, we discovered repeated destabilisation of the intracellular loop 1 (ICL1) upon full agonist binding and stabilisation upon antagonist binding, suggesting that increased dynamics in this region are an essential component for G protein recruitment. Multiple sequence alignments and molecular dynamics simulations indicate that L72 in ICL1 plays an important structural role. Differential HDX-MS experiment of tβ1AR and tβ1AR L72A construct in complex with miniGs, in response to various ligands, suggests involvement of ICL1 in stabilising the GDP bound state by influencing the stability of HG helix of miniGs.