Abstract
We have determined the 3.2 Å 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.
Original language | English (US) |
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Pages (from-to) | 317-328 |
Number of pages | 12 |
Journal | Cancer cell |
Volume | 5 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2004 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research