Details

Autor(en) / Beteiligte

• Needham, Sarah R.
• Roberts, Selene K.
• Arkhipov, Anton
• Mysore, Venkatesh P.
• Tynan, Christopher J.
• Zanetti-Domingues, Laura C.
• Kim, Eric T.
• Losasso, Valeria
• Korovesis, Dimitrios
• Hirsch, Michael
• Rolfe, Daniel J.
• Clarke, David T.
• Winn, Martyn D.
• Lajevardipour, Alireza
• Clayton, Andrew H. A.
• Pike, Linda J.
• Perani, Michela
• Parker, Peter J.
• Shan, Yibing
• Shaw, David E.
• Martin-Fernandez, Marisa L.

Titel

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Ist Teil von

• Nature communications, 2016-10, Vol.7 (1), p.13307-13307, Article 13307

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling. Epidermal growth factor receptors have been shown to oligomerise upon binding to their cognate ligands. Here, the authors use biochemical, biophysical and cell biology techniques to analyse the structures of these oligomers, and argue that these formations are required for signalling.