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CPLC/iPoLS Seminar: Emmanuel Margeat "Exploring G-protein coupled receptors structure, dynamics, and assemblies with single molecule fluorescence"

9/13/2018 10:50:27 AM CPLC Staff

Metabotropic glutamate receptors (mGluRs) are multidomain proteins belonging to class C G-protein coupled receptors (GPCR). These membrane proteins are essential in controlling synaptic transmission, and as such are important drug targets for the treatment of several disorders including pain, Parkinson’s disease, schizophrenia, …

I will cover in this presentation our recent efforts to investigate the conformational changes, oligomerization, and allosteric transitions associated with mGluR activation.

First, I will present how we used in vitro single molecule FRET to demonstrate that the receptor ligand binding domain oscillates between a resting and an active state in a submillisecond timescale. The role of ligand binding will be elucidated, and especially the action of partial agonists, that do not fully activate the receptor despite their high affinity.

Then, I will present our results on the oligomerization of mGluRs in living neurons. I will show the ability of a fluorescence fluctuation microscopy method (scanning Number & Brightness) to quantify these receptor’s oligomeric state. The role of ligands on promoting this oligomerization will be demonstrated.

Finally I will present our model proposing that the fast structural dynamics of the receptor in the apo state precludes its oligomerization, that is triggered by the binding of ligands stabilizing either the active or the resting state.

 

Réferences

Olofsson et al., Nature Communications, 2014, 5, 5206.

Møller et al., Scientific Reports, 2018, 8(1):10414.

1/22/2014

LaserFocusWorld (Tulsa, Okla., Jan. 22) -- White-light diffraction tomography, a new imaging technique developed at Illinois, needs no dyes or other chemicals, yet renders high-resolution 3-D quantitative imagery of cells and their internal structures – all with conventional microscopes and white light. The team of U. of I. researchers, led by electrical and computer engineering and bioengineering professor Gabriel Popescu, published their work in Nature Photonics. Also: The Huffington Post UK (Jan. 23), California Institute for Regenerative Medicine (San Francisco, Feb. 5).