N -Glycosylation as determinant of epidermal growth factor receptor conformation in membranes

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Abstract
Significance: Structural analysis of growth factor receptors in their membrane environment is key for understanding their functions that are vital to the development and survival of organisms. High structural flexibility and posttranslational modifications of the full-length receptors, however, hinder structural analysis at high resolution. Here, we used atomistic molecular dynamics simulations and biochemical experiments with proteoliposomes to elucidate the role of N -glycosylation with regard to the structural properties of the human epidermal growth factor receptor (EGFR). We find that N -glycosylation critically determines membrane interactions and structural arrangement of the ligand-binding EGFR ectodomain. This combined approach provides new means to structurally explore and experimentally validate functional properties of cell surface receptors and test therapeutic agents, such as monoclonal antibodies.

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