1YY9

Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225

1YY9 の概要

• エントリーDOI: 10.2210/pdb1yy9/pdb
• 関連するPDBエントリー: 1YY8
• 分子名称: Epidermal Growth Factor Receptor, Cetuximab Fab Light chain, Cetuximab Fab Heavy chain, ... (7 entities in total)
• 機能のキーワード: cell surface receptor; tyrosine kinase; glycoprotein; antigen:antibody complex; fab fragment; antitumor; drug, immune system-transferase complex, immune system/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 120235.81

構造登録者

Li, S.,Schmitz, K.R.,Jeffrey, P.D.,Wiltzius, J.J.W.,Kussie, P.,Ferguson, K.M. (登録日: 2005-02-24, 公開日: 2005-04-26, 最終更新日: 2024-11-13)

主引用文献

Li, S.,Schmitz, K.R.,Jeffrey, P.D.,Wiltzius, J.J.W.,Kussie, P.,Ferguson, K.M.
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab
Cancer Cell, 7:301-311, 2005

PubMed Abstract: Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation.

PubMed: 15837620
DOI: 10.1016/j.ccr.2005.03.003

実験手法

X-RAY DIFFRACTION (2.605 Å)