1NQL

Structure of the extracellular domain of human epidermal growth factor (EGF) receptor in an inactive (low pH) complex with EGF.

1NQL の概要

• エントリーDOI: 10.2210/pdb1nql/pdb
• 分子名称: epidermal growth factor receptor, epidermal growth factor, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: cell surface receptor, tyrosine kinase, glycoprotein, endosomal, growth factor, auto-inhibition, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78146.34

構造登録者

Ferguson, K.M.,Lemmon, M.A. (登録日: 2003-01-21, 公開日: 2003-03-11, 最終更新日: 2024-12-25)

主引用文献

Ferguson, K.M.,Berger, M.B.,Mendrola, J.M.,Cho, H.,Leahy, D.J.,Lemmon, M.A.
EGF activates its receptor by removing interactions that auto-inhibit ectodomain dimerization
Mol.Cell, 11:507-517, 2003

PubMed Abstract: Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER) family receptor tyrosine kinases (RTKs), which regulate cell growth and differentiation and are implicated in many human cancers. EGF activates its receptor by inducing dimerization of the 621 amino acid EGF receptor extracellular region. We describe the 2.8 A resolution crystal structure of this entire extracellular region (sEGFR) in an unactivated state. The structure reveals an autoinhibited configuration, where the dimerization interface recently identified in activated sEGFR structures is completely occluded by intramolecular interactions. To activate the receptor, EGF binding must promote a large domain rearrangement that exposes this dimerization interface. This contrasts starkly with other RTK activation mechanisms and suggests new approaches for designing ErbB receptor antagonists.

PubMed: 12620237
DOI: 10.1016/S1097-2765(03)00047-9

実験手法

X-RAY DIFFRACTION (2.8 Å)