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Biological Physics Seminar (iPoLS): "Exploring G-protein coupled receptors structure, dynamics, and assemblies with single molecule fluorescence"

Event Type
Seminar/Symposium
Sponsor
Department of Physics
Location
144 Loomis
Date
Sep 14, 2018   2:00 pm  
Speaker
Emmanuel Margeat, Centre de Biochimie Structurale at CNRS, Montpellier, France
Contact
Becky McDuffee
E-Mail
mcduffbe@illinois.edu
Phone
217-300-0898
Views
18
Originating Calendar
Physics - Biological Physics (CPLC/iPoLS) Seminar

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.

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