DOI: 10.1101/458265Oct 31, 2018Paper

In-Cell Structural Dynamics of an EGF Receptor during Ligand-induced Dimer-Oligomer Transition.

BioRxiv : the Preprint Server for Biology
Andrew H A Clayton, Noga Kozer

Abstract

The epidermal growth factor receptor (EGFR) is a membrane protein that regulates cell proliferation, differentiation and survival, and is a drug target for cancer therapy. Ligand-induced activation of the EGFR kinase is generally regarded to require ligand-bound-dimers, while phosphorylation and down-stream signalling is modulated by higher-order oligomers. Recent work has unveiled changes in EGFR dynamics from ligand-induced dimerization in membranes extracted from cells, however less is known about the changes in EGFR dynamics that accompany the ligand-induced dimer to tetramer transition in a live cell environment. In the present report, we determine the dynamics of a c-terminal GFP tag attached to EGFR in the unliganded dimer and in the liganded tetramer by means of dynamic depolarization microscopy. We made use of a novel analysis method, the single-frequency polarized phasor ellipse approach, to extract two correlation times on the sub-nanosecond and super-nanosecond timescales, respectively. EGF binding to the EGFR-GFP dimer lengthened the sub-nanosecond correlation time (from 0.1ns to 1.3ns), and shortened the super-nanosecond correlation time (from 210ns to 56ns) of the c-terminal GFP probe. The sub-nanosecond depolari...Continue Reading

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