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

来源：

CELL | 2002年 / 110卷 / 06期

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

页码：775 / 787

页数：13

共 62 条

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