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. Author manuscript; available in PMC: 2011 Feb 8.
Published in final edited form as: Trends Mol Med. 2007 Nov 5;13(12):527–534. doi: 10.1016/j.molmed.2007.10.002

Figure 1. The structural basis for the activation of HER proteins.

Figure 1

The extracellular regions of HER proteins are composed of four domains numered I,II,III, and IV. Domains I and III are ligand binding domains, and domains II and IV are cysteine-rich domains which bind each other and other receptors. The tyrosine kinase domain has two lobes which are shared among the tyrosine kinase family and are termed the n-terminal and c-terminal lobes. The c-terminal tail contains many tyrosines which are targets for phosphorylation. When unliganded, the ECD is folded into a closed conformation due to an intramolecular interaction between domains II and IV (see inactive monomer). The HER ligand bind domains I and III bringing them together. The result is a refolding that exposes domain II which is the dimerization interface (see active monomer). The dimerization domains of two active receptors interact, bring the intracellular domains in close proximity and the interaction of the two kinase domains results in transphosphorylation (see dimer).