Figure 9. Modeling of MHR interaction with Ack1.

(A) Partial sequence alignment of the MIG6 sequence with its homologous region in Ack1 protein. The residue identities are highlighted. Emphasis is on the part of the MIG6 sequence that has been modeled in MIG6-EGFR complex structure [27]. MIG6 residues present in the model are underlined. (B) The MIG6 fragment (corresponding to residues 805–831 of MHR) present in EGFR is modeled onto the inactive state structure of Ack1 kinase domain+SH3 domain structure. The SH3 domain is shown in surface representation. The substrate peptide binding site, as surmised from other SH3-peptide complex structures, is highlighted in deep orange shade. The MIG6 fragment, as bound to EGFR kinase domain, would present a steric conflict near its N-terminal end with the SH3 domain, as can be seen in the figure.