Conformational stability of the epidermal growth factor (EGF) receptor as influenced by glycosylation,dimerization and EGF hormone binding |
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| Authors: | Eric S Taylor Laercio Pol‐Fachin Roberto D Lins Steven K Lower |
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| Affiliation: | 1. Department of Geology, Kent State University, North Canton, Ohio;2. Aggeu Magalh?es Research Center, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil;3. Department of Fundamental Chemistry, Federal University of Pernambuco, Recife, Pernambuco, Brazil;4. School of Environment and Natural Resources, Ohio State University, Columbus, Ohio |
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| Abstract: | The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N‐glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF–EGFR binding takes place through a large‐scale induced‐fitting mechanism. Proteins 2017; 85:561–570. © 2016 Wiley Periodicals, Inc. |
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| Keywords: | ErbB glycoprotein molecular dynamics EGF binding |
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