Author/Authors :
Hideo Ogiso، نويسنده , , Ryuichiro Ishitani، نويسنده , , Osamu Nureki، نويسنده , , Shuya Fukai، نويسنده , , Mari Yamanaka، نويسنده , , Jae-Hoon Kim، نويسنده , , Kazuki Saito، نويسنده , , Ayako Sakamoto، نويسنده , , Mio Inoue، نويسنده , , Mikako Shirouzu، نويسنده , , Shigeyuki Yokoyama، نويسنده ,
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 Å 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 β-hairpin arm of each domain II holds the body of the other. The unique “receptor-mediated dimerization” was verified by EGFR mutagenesis.
