Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.
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.
Ogiso
Hideo
H
RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, 230-0045, Yokohama, Kanagawa, Japan.
Ishitani
Ryuichiro
R
Nureki
Osamu
O
Fukai
Shuya
S
Yamanaka
Mari
M
Kim
Jae-Hoon
JH
Saito
Kazuki
K
Sakamoto
Ayako
A
Inoue
Mio
M
Shirouzu
Mikako
M
Yokoyama
Shigeyuki
S
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism*; D066246:ErbB Receptors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012643:Selenium / Q000737:chemistry; D017422:Sequence Analysis, DNA
D024322:Amino Acids, Aromatic; D004220:Disulfides; D008024:Ligands; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D012643:Selenium