3C09

Crystal structure the Fab fragment of matuzumab (Fab72000) in complex with domain III of the extracellular region of EGFR

Summary for 3C09

• Entry DOI: 10.2210/pdb3c09/pdb
• Related: 3C08
• Descriptor: Matuzumab Fab Light chain, Matuzumab Fab Heavy chain, Epidermal growth factor receptor, ... (6 entities in total)
• Functional Keywords: cell surface receptor, glycoprotein, antigen, antibody complex, fab fragment, antitumor, drug immune system-transferase complex, immune system-transferase complex, immune system/transferase
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 144883.62

Authors

Ferguson, K.M.,Schmiedel, J.,Knoechel, T. (deposition date: 2008-01-18, release date: 2008-04-15, Last modification date: 2023-11-01)

Primary citation

Schmiedel, J.,Blaukat, A.,Li, S.,Knochel, T.,Ferguson, K.M.
Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.
Cancer Cell, 13:365-373, 2008

PubMed Abstract: An increasing number of therapeutic antibodies targeting tumors that express the epidermal growth factor receptor (EGFR) are in clinical use or late stages of clinical development. Here we investigate the molecular basis for inhibition of EGFR activation by the therapeutic antibody matuzumab (EMD72000). We describe the X-ray crystal structure of the Fab fragment of matuzumab (Fab72000) in complex with isolated domain III from the extracellular region of EGFR. Fab72000 interacts with an epitope on EGFR that is distinct from the ligand-binding region on domain III and from the cetuximab/Erbitux epitope. Matuzumab blocks ligand-induced receptor activation indirectly by sterically preventing the domain rearrangement and local conformational changes that must occur for high-affinity ligand binding and receptor dimerization.

PubMed: 18394559
DOI: 10.1016/j.ccr.2008.02.019

Experimental method

X-RAY DIFFRACTION (3.2 Å)