Journal article
Ligand binding induces a conformational change in epidermal growth factor receptor dimers
F Walker, J Rothacker, C Henderson, EC Nice, B Catimel, HH Zhang, AM Scott, MF Bailey, SG Orchard, TE Adams, Z Liu, TPJ Garrett, AHA Clayton, AW Burgess
Growth Factors | Published : 2012
Abstract
The activation of the epidermal growth factor receptor (EGFR) kinase requires ligand binding to the extracellular domain (ECD). Previous reports demonstrate that the EGFR-ECD can be crystallized in two conformations-a tethered monomer or, in the presence of ligand, an untethered back-to-back dimer. We use Biosensor analysis to demonstrate that even in the monomeric state different C-terminal extensions of both truncated (EGFR1-501)-ECD and full-length EGFR1-621-ECD can change the conformation of the ligand-binding site. The binding of a monoclonal antibody mAb806, which recognizes the dimer interface, to the truncated EGFR1-501-Fc fusion protein is reduced in the presence of ligand, consiste..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This project was partially funded by NHMRC Program Grant 487922 'Colorectal cancer - molecular basis to targeted therapeutics' and by funds from the Operational Infrastructure Support Program provided by the Victorian Government, Australia. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. In addition, the manuscript is solely the responsibility of the institutions and individual authors and does not reflect the views of NHMRC. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.