Negative co-operativity in the EGF receptor

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Scatchard analyses of the binding of EGF (epidermal growth factor) to its receptor (EGFR) yield concaveup Scatchard plots, indicative of some type of heterogenity in ligand-binding affinity. This was typically interpreted as being due to the presence of two independent binding sites: one of high affinity representing ≤10% of the receptor population, and one of low affinity making up the bulk of the receptors. However, the concept of two independent binding sites is difficult to reconcile with the X-ray structures of the dimerized EGFR that show symmetrical binding of the two ligands. A new approach to the analysis of 125IEGF- binding data combined with the structure of the singly-occupied Drosophila EGFR have now shown that this heterogeneity is due to the presence of negative co-operativity in the EGFR. Concerns that negative co-operativity precludes ligand-induced dimerization of the EGFR confuse the concepts of linkage and cooperativity. Linkage refers to the effect of ligand on the assembly of dimers, whereas co-operativity refers to the effect of ligand binding to one subunit on ligand binding to the other subunit within a preassembled dimer. Binding of EGF to its receptor is positively linked with dimer assembly, but shows negative cooperativity within the dimer.

Original languageEnglish
Pages (from-to)15-19
Number of pages5
JournalBiochemical Society transactions
Issue number1
StatePublished - Feb 2012


  • Epidermal growth factor (EGF)
  • Epidermal growth factor receptor (EGFR)
  • Negative co-operativity
  • Saturation binding isotherm


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