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Mercredi 1 Juillet 2020
De 16h à 17h
Centre de recherche - Paris - Webinar

Single-molecule investigation of nanoscale conformations in human epidermal growth factor receptors

Membrane receptors control fundamental cellular processes ranging from gene expression to apoptosis. Nearly 30% of the human genome encodes membrane proteins, and about 60% of known drugs target the membrane proteins. Mechanistic understanding of membrane receptors and their structural re-organization upon ligand (and drug) binding leading to a variety of cellular processes has both scientific and industrial significance.
In this talk, I will discuss the signal transduction mechanism across full-length human epidermal growth factor receptor (EGFR) which is a major target of anti-cancer drugs. We employ cell-free expression to isolate functional monomeric EGFR within a membrane nanodisc, a lipid bilayer encircled by a belting protein.  Using a multidisciplinary approach involving single-molecule Förster resonance energy transfer and mutagenesis, we identify intracellular conformations of full-length EGFR upon extracellular ligand and drug binding. I will further talk about the impact of phosphorylation on the conformations of the intrinsically disordered carboxyl-terminus domain of EGFR. These findings have implications in the formation of signaling complexes and in protein biophysics, in general.



Raju Regmi

Laser Biomedical Research Center, Massachusetts Institute of Technology, USA

Invité(e)(s) par

Patricia Bassereau