Extracellular EGFR (ErbB1)

In the absence of ligand EGFR, ErbB3, and ErbB4 adopt an inactive confirmation where the dimerization arm, a portion of the cysteine-rich subdomain CR1 (green), is blocked by interactions with the CR2 subdomain (red). Ligand binding to the leucine rich domains L1 (blue) and L2 (yellow) causes an allosteric change revealing the dimerization arm which will allow the intracellular tyrosine kinase domains to autophosphorylate upon homo- or heterodimer formation.

Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ, Lemmon MA. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol. Cell. 2003;11(2):507-517. PMID: 12620237

1NQL (PDB)

Extracellular HER2 (ErbB2)

Unlike all other ErbB receptors, a high-affinity ligand for HER2 has not been found suggesting HER2 activation may not be regulated by ligand binding. The dimerization arm within CR1 (green) does not make contact with CR2 (red) so it may be available for dimerization and subsequent tyrosine kinase activation, regardless of ligand concentration. 

Choo HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW, Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with Herceptin Fab. Nature 2003;421(6924):451-4260. PMID: 12610629

1S78 (PDB)