2. Academic Validation
  3. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains

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.
Hideo Ogiso 1,  Ryuichiro Ishitani,  Osamu Nureki,  Shuya Fukai,  Mari Yamanaka,  Jae-Hoon Kim,  Kazuki Saito,  Ayako Sakamoto,  Mio Inoue,  Mikako Shirouzu,  Shigeyuki Yokoyama
Affiliations

Affiliation

  • 1 RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, 230-0045, Yokohama, Kanagawa, Japan.
PMID: 12297050 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.

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