Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.
Article Details
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Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX
Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.
Cancer Cell. 2004 Apr;5(4):317-28.
- PubMed ID
- 15093539 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Pertuzumab Receptor tyrosine-protein kinase erbB-2 Protein Humans YesBinderAntibodyDetails - Polypeptides
Name UniProt ID Receptor tyrosine-protein kinase erbB-2 P04626 Details Uncharacterized protein Q7Z3Y4 Details