Human Epidermal Growth Factor Receptor (EGFR) Aligned on the Plasma Membrane Adopts Key Features of Drosophila EGFR Asymmetry

• DOI: 10.1128/mcb.01431-10
• Publication Date: 2011-03-29T02:09:02Z
• Authors: Christopher J. Tynan; Selene K. Roberts; Daniel J. Rolfe; David T. Clarke; Hannes H. Loeffler; Johannes Kästner; Martyn D. Winn; Peter J. Parker; Marisa L. Martin-...
• Keywords: Cooperativity

The ability of epidermal growth factor receptor (EGFR) to control cell fate is defined by its affinity for ligand. Current models suggest that ligand-binding heterogeneity arises from negative cooperativity in signaling dimers, which the asymmetry extracellular region Drosophila EGFR has recently provided a structural basis. However, no apparent isolated human EGFR. Human also differs found only full-length receptors cells. To gain insights into situ, we developed an approach based on quantitative Förster resonance energy transfer (FRET) imaging, combined with Monte Carlo and molecular dynamics simulations, probe conformation epithelial We experimentally demonstrate high-affinity consistent aligned flat plasma membrane. explored relevance this structure shares key features EGFR, suggesting basis conserved invertebrates humans but requires interactions