Invité équipe Y. Bourne/P. Marchot: Jonathan Elegheert, IINS, Bordeaux, France – “Unlocking structural studies of transient neuronal protein-protein interactions using a combination of technical innovations”

Résumé

Fast excitatory signal transmission in the central nervous system is initiated by the ionotropic glutamate receptors (iGluRs). These receptors are located in the post-synaptic membrane and respond to the release of the neurotransmitter glutamate by opening their cation-conductive pore, leading to an influx of sodium ions and membrane depolarisation.

                  iGluRs are stabilized at synapses in response to synaptic activity. However, structural insights into how these receptors interact with extracellular protein interaction partners is lacking due to their very weak interaction affinities.

                  I will present how we use lentiviral transduction of mammalian cells for large-scale protein production, biophysical methods (SPR, BLI, MALS, AUC, etc.) for protein-protein interaction analysis, in vitro molecular evolution for affinity maturation of transient interactions, and single-particle cryo-EM for high-resolution structure determination.

                  Together, these techniques unlock structural studies of synaptic iGluR complexes, yielding molecular insights into the molecular processes that underpin synaptic signaling.