1. Sensing membrane protein activation and modulation in a high- throughput format FRET assay

GPCRs undergo large conformational changes during their activation. Starting from existing Xray structures in the PDB, we used Normal Modes Analyses (NMA) to study the collective motions of the agonist-bound β2-adrenergic receptor both in its isolated "uncoupled" and Gprotein "coupled" conformations. We interestingly observed that the receptor was able to adopt only one major motion in the protein:protein complex. This motion corresponded to an antisymmetric rotation of both its extra- and intra-cellular parts, with a key role of previously identified highly conserved proline residues. Because this motion was also retrieved when performing NMA on 7 other GPCRs which structures were available, it is strongly suspected to possess a significant biological role, possibly being the "activation mode" of a GPCR when coupled to Gproteins.