Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface.

Crystal structures of complexes between the epidermal growth factor receptor (EGFR) kinase domain and a fragment of its feedback inhibitor MIG6 reveal an allosteric inhibition mechanism. MIG6 binds the cyclin/CDK-like asymmetric dimer interface of EGFR and blocks formation of the activating dimer.