Fig. 1
From: The architecture of EGFR’s basal complexes reveals autoinhibition mechanisms in dimers and oligomers
Models of ligand-free and ligand-bound EGFR complexes. a Top left: Cartoon of an EGFR monomer5. Top right: A ligand-bound back-to-back extracellular dimer8,9. This is linked to the catalytically active asymmetric TKD (aTKD) dimer10 by an N-terminal crossing transmembrane (TM) dimer40 and an antiparallel juxtamembrane-A (JM-A) helical dimer22. b Cartoon of the extracellular portion and TM domains of ligand-bound EGFR polymers formed by alternating back-to-back and face-to-face interfaces12. Two EGF molecules are bound at the end-receptors capping the polymer chain with a 2N:2 receptor/ligand stoichiometry. An 8:2 octamer is shown (intracellular regions not depicted). c Cartoon of a speculative ligand-free side-to-side dimer that would putatively combine the double autoinhibition of a tethered extracellular domain and a symmetric tyrosine kinase domain (sTKD) dimer5,20,22. d Cartoon of a ligand-free extended back-to-back dimer coupled via a TM domain C-crossing dimer to an sTKD dimer (modified from Arkhipov et al.23). e Cartoon of a stalk-to-stalk tethered dimer coupled via an N-crossing TM domain dimer to the aTKD dimer induced by TKI binding in the C-terminal domain truncated Δ998-EGFR (modified from Lu et al.26). For all panels ECM domains I and III are in red, II and IV in blue, EGF ligand is in green, plasma membrane in yellow, TM in teal, JM in dark grey, TKD in light grey
