Title : Insights into
ErbB signaling from the structure of the
ErbB2-pertuzumab complex
Abstract :
- We have determined the 3.2 A X-ray crystal structure of the extracellular domain of the human epidermal growth factor receptor 2 ( ErbB2 or HER2 ) in a complex with the antigen binding fragment of pertuzumab, an anti- ErbB2 monoclonal antibody also known as 2C4 or Omnitarg
- Pertuzumab binds to ErbB2 near the center of domain II, sterically blocking a binding pocket necessary for receptor dimerization and signaling
- The ErbB2-pertuzumab structure, combined with earlier mutagenesis data, defines the pertuzumab residues essential for ErbB2 interaction
- To analyze the ErbB2 side of the interface, we have mutated a number of residues contacting pertuzumab and examined the effects of these mutations on pertuzumab binding and ErbB2- ErbB3 heterodimerization
- We have also shown that conserved residues previously shown to be necessary for EGF receptor homodimerization may be dispensible for ErbB2- ErbB3 heterodimerization