Scatchard analyses of the binding of EGF (epidermal growth factor) to its receptor (EGFR) yield concave up 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 125I-EGF-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 co-operativity. 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 co-operativity within the dimer.
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February 2012
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Conference Article|
January 19 2012
Negative co-operativity in the EGF receptor
Linda J. Pike
Linda J. Pike
1
1Washington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 So. Euclid, Box 8231, St. Louis, MO 63110, U.S.A.
1email pike@biochem.wustl.edu
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Publisher: Portland Press Ltd
Received:
May 31 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (1): 15–19.
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Received:
May 31 2011
Citation
Linda J. Pike; Negative co-operativity in the EGF receptor. Biochem Soc Trans 1 February 2012; 40 (1): 15–19. doi: https://doi.org/10.1042/BST20110610
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