Epitopes described in "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex."

Article Authors:Matthew C Franklin; Kendall D Carey; Felix F Vajdos; Daniel J Leahy; Abraham M de Vos; Mark X Sliwkowski
Article Title:Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.
Reference Detail
Reference ID:465
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.
Affiliations:Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94114 USA.
Reference Type:Literature
PubMed ID:15093539
Journal:Cancer Cell
Journal Volume:5
Article Pages:317-28
Journal ISSN:1878-3686
Article Chemical List:Antibodies, Monoclonal;Antibodies, Monoclonal, Humanized;Ligands;pertuzumab;Receptor, ErbB-2
Article MeSH List:Animals; Antibodies, Monoclonal(chemistry; genetics; metabolism); Antibodies, Monoclonal, Humanized; Binding Sites; Binding Sites, Antibody; CHO Cells; Cricetinae; Crystallography, X-Ray; Dimerization; Humans; Ligands; Models, Molecular; Mutagenesis, Site-Directed; Protein Structure, Tertiary; Receptor, ErbB-2(chemistry; genetics; metabolism); Signal Transduction
Article Comments:15093533 Cancer Cell. 2004 Apr;5(4):299-301
Curation Last Updated:2015-06-05 00:10:33