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| Article Authors: | Matthew C Franklin; Kendall D Carey; Felix F Vajdos; Daniel J Leahy; Abraham M de Vos; Mark X Sliwkowski |
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| Article Title: | Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. |
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| Reference ID: | 465 |
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| 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. |
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| Affiliations: | Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94114 USA. |
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| Date: | 2004 |
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| Reference Type: | Literature |
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| PubMed ID: | 15093539 |
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| Journal: | Cancer Cell |
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| Journal Volume: | 5 |
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| Article Pages: | 317-28 |
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| Journal ISSN: | 1535-6108 |
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| Article Chemical List: | Antibodies, Monoclonal;Binding Sites, Antibody;Ligands;pertuzumab;Receptor, erbB-2 |
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| Article MeSH List: | Animals; Antibodies, Monoclonal(chemistry; genetics; metabolism); 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 |
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| Article Comments: | 15093533 Cancer Cell. 2004 Apr;5(4):299-301 |
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| Curation Last Updated: | 2012-05-31 20:01:48 |
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