Activation of the epidermal growth factor receptor: a series of twists and turns

Poger, David and Mark, Alan E. (2014) Activation of the epidermal growth factor receptor: a series of twists and turns. Biochemistry, 53 16: 2710-2721. doi:10.1021/bi401632z


Author Poger, David
Mark, Alan E.
Title Activation of the epidermal growth factor receptor: a series of twists and turns
Journal name Biochemistry   Check publisher's open access policy
ISSN 1520-4995
0006-2960
1943-295X
Publication date 2014-04-29
Year available 2014
Sub-type Article (original research)
DOI 10.1021/bi401632z
Open Access Status
Volume 53
Issue 16
Start page 2710
End page 2721
Total pages 12
Place of publication Washington DC, United States
Publisher American Chemical Society
Collection year 2015
Language eng
Abstract The cell surface epidermal growth factor receptor (EGFR) plays a critical role in cell development and oncogenesis. The binding of growth factors to the EGFR results in a mechanical signal being transmitted through the plasma membrane. In this study, atomistic molecular dynamics simulations have been used to investigate the conformational changes associated with the binding of the epidermal growth factor (EGF) and transforming growth factor α (TGFα) to the EGFR. In the simulations, the removal of the EGF and TGFα from the extracellular domain of the EGFR homodimer led to a relative rotation of the protomers of 16-35° about the dimerization axis. The three N-terminal domains that make up the extracellular region of the receptor undergo essentially rigid-body motion. The dimerization interface itself was found to be largely unaffected by the removal of the ligand. In most simulations, the rotation within the dimer was associated with an opening of the cytokine-binding sites. On the basis of these simulations, a simple mechanical model that explains the coupling between the binding of ligand and the motions in the extracellular domains is proposed.
Keyword Cell membranes
Dimerization
Dimers
Ligands
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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