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

被引:933
作者
Ogiso, H
Ishitani, R
Nureki, O
Fukai, S
Yamanaka, M
Kim, JH
Saito, K
Sakamoto, A
Inoue, M
Shirouzu, M
Yokoyama, S
机构
[1] RIKEN, Genom Sci Ctr, Yokohama, Kanagawa 2300045, Japan
[2] Japan Sci & Technol Corp, ERATO, Yokoyama CytoLog Project, Tokyo, Japan
[3] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan
[4] SPring 8, Harima Inst, RIKEN, Cellular Signaling Lab, Sayo, Hyogo 6795148, Japan
[5] SPring 8, Harima Inst, RIKEN, Structurome Grp, Sayo, Hyogo 6795148, Japan
关键词
D O I
10.1016/S0092-8674(02)00963-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Angstrom 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.
引用
收藏
页码:775 / 787
页数:13
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