1S78

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

Summary for 1S78

• Entry DOI: 10.2210/pdb1s78/pdb
• Related: 1L7I 1N8Y 1N8Z
• Descriptor: Receptor protein-tyrosine kinase erbB-2, Pertuzumab Fab light chain, Pertuzumab Fab heavy chain, ... (6 entities in total)
• Functional Keywords: receptor-antibody complex, fab fragment, cysteine-rich domain, leucine-rich repeat, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 235727.05

Authors

Franklin, M.C.,Carey, K.D.,Vajdos, F.F.,Leahy, D.J.,de Vos, A.M.,Sliwkowski, M.X. (deposition date: 2004-01-29, release date: 2004-04-27, Last modification date: 2024-10-30)

Primary citation

Franklin, M.C.,Carey, K.D.,Vajdos, F.F.,Leahy, D.J.,De Vos, A.M.,Sliwkowski, M.X.
Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.
Cancer Cell, 5:317-328, 2004

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.

PubMed: 15093539
DOI: 10.1016/S1535-6108(04)00083-2

Experimental method

X-RAY DIFFRACTION (3.25 Å)