Study of the energy landscape of G protein-coupled receptors
Most hormones and neurotransmitters communicate information to cells via G protein coupled receptors (GPCRs). The large number of biological functions they control also makes these membrane receptors one of the most important families of pharmacological targets in biomedicine. GPCRs are considered to be flexible and dynamic proteins per se, i.e. they can visit several conformational states linked to distinct biological outcomes. Despite a very large number of structures at the atomic scale that are regularly published, these data must be completed to fully understand the function of these complex allosteric machines. The project aims at characterizing the energy landscape of these receptors in complement to low-energy and highly populated published atomic structures by advanced biophysical methods: NMR (kinetic barriers and conformational ensembles), electron cryo-microscopy (structural aspects & conformational ensembles) and single molecule force spectroscopy (kinetics of interactions between ligands and/or effectors with receptors).
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