The peptide derived from erbB2 auto-inhibitor herstatin shared in the same epitope and function with functional antibody 2C4.

Previous studies have shown that different epitopes of HER2 exhibit distinct functions and that the epitope bound by the antibody 2C4 plays a role in formation of hetereodimers between HER2 and other receptors of the HER family. In this study, we used computer modeling to determine that the epitope of HER2 which the C-terminal 79 amino acids of herstatin (named HSTC79) binds is similar to that bound by 2C4. Based on these theoretical results, recombinant HSTC79 fused with GST was expressed in Escherichia coli and purified by affinity chromatography. Experimental analysis showed that HSTC79 did specifically bind to HER2 and that the epitope of HER2 identified by HSTC79 was near that identified by 2C4. Furthermore, HSTC79 inhibited the growth of HER2-overexpressing cells. These results highlight the fact that the binding site architecture and certain key residues of HER2 may be very helpful for understanding the protein's biological role and providing insights for designing novel inhibitors of HER2.