Fig. 8
From: The architecture of EGFR’s basal complexes reveals autoinhibition mechanisms in dimers and oligomers
Cartoon models of ligand-free EGFR species on the cell surface. a, b Autoinhibited ligand-free receptors form a dimers and b larger oligomers via extracellular head-to-head interactions. Within head-to-head dimers and oligomers the ICMs remain as non-interacting units. c, d Kinase-mediated receptor dimerisation outcompetes head-to-head interactions to form two types of receptor dimers that typically coexist in equilibrium (bearing aTKD and sTKD dimer configurations). Head-to-head dimers and oligomers are disrupted by kinase-mediated dimerisation independently of whether the driver mutation and/or treatment is activating or not. The ECM architecture of one dimer type is consistent with a back-to-back dimer and structurally coupled to an sTKD dimer6,22 (c). The ECM architecture of the other is consistent with a stalk-to-stalk dimer and structurally coupled via an N-terminal TM crossing to the aTKD dimer40 (d). The L680N kinase domain mutation shifts the equilibrium toward the dimer population bearing sTKD dimers while L834R shifts the equilibrium towards the dimer population bearing the aTKD dimer. For all panels, DI is in green, DII in red, DIII in blue, DIV, TMD and JMD in grey, TKD in silver
