Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains

Cell. 2002 Sep 20;110(6):775-87. doi: 10.1016/s0092-8674(02)00963-7.

Abstract

Epidermal growth factor (EGF) regulates cell proliferation and differentiation by binding to the EGF receptor (EGFR) extracellular region, comprising domains I-IV, with the resultant dimerization of the receptor tyrosine kinase. In this study, the crystal structure of a 2:2 complex of human EGF and the EGFR extracellular region has been determined at 3.3 A resolution. EGFR domains I-III are arranged in a C shape, and EGF is docked between domains I and III. The 1:1 EGF*EGFR complex dimerizes through a direct receptor*receptor interaction, in which a protruding beta-hairpin arm of each domain II holds the body of the other. The unique "receptor-mediated dimerization" was verified by EGFR mutagenesis.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Aromatic / chemistry
  • Animals
  • Binding Sites
  • CHO Cells
  • Cricetinae
  • Crystallization
  • Crystallography, X-Ray
  • Dimerization
  • Disulfides / chemistry
  • Epidermal Growth Factor / chemistry*
  • Epidermal Growth Factor / metabolism*
  • ErbB Receptors / chemistry*
  • ErbB Receptors / metabolism*
  • Humans
  • Ligands
  • Models, Molecular*
  • Molecular Structure
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Selenium / chemistry
  • Sequence Analysis, DNA

Substances

  • Amino Acids, Aromatic
  • Disulfides
  • Ligands
  • Epidermal Growth Factor
  • ErbB Receptors
  • Selenium

Associated data

  • PDB/1IVO