1NQL

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

Summary for 1NQL

• Entry DOI: 10.2210/pdb1nql/pdb
• Descriptor: 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)
• Functional Keywords: cell surface receptor, tyrosine kinase, glycoprotein, endosomal, growth factor, auto-inhibition, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 78146.34

Authors

Ferguson, K.M.,Lemmon, M.A. (deposition date: 2003-01-21, release date: 2003-03-11, Last modification date: 2024-12-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)