Binding of single-mutant epidermal growth factor (EGF) ligands alters the stability of the EGF receptor dimer and promotes growth signaling.

ABSTRACT: The epidermal growth factor receptor (EGFR) is a membrane-anchored tyrosine kinase that is able to selectively respond to multiple extracellular stimuli. Previous studies have indicated that the modularity of this system may be caused by ligand-induced differences in the stability of the receptor dimer. However, this hypothesis has not been explored using single-mutant ligands thus far. Herein, we developed a new approach to identify residues responsible for functional divergence by selecting residues in the epidermal growth factor (EGF) ligand that are conserved among orthologs yet divergent between paralogs. Then, we mutated these residues and assessed the mutants' effects on the receptor using a combination of molecular dynamics (MD) and biochemical techniques. Although the EGF mutants

SUBMITTER: Pascarelli S 

PROVIDER: S-EPMC8259408 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature