Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.

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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	Yes	Binder Antibody	Details

Polypeptides

Name	UniProt ID
Receptor tyrosine-protein kinase erbB-2	P04626	Details
Uncharacterized protein	Q7Z3Y4	Details