title: Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.
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.
authors.affiliation: RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, 230-0045, Yokohama, Kanagawa, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ogiso
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishitani
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
authors.forename: Shuya
authors.initials: S
authors.lastname: Fukai
authors.forename: Mari
authors.initials: M
authors.lastname: Yamanaka
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kazuki
authors.initials: K
authors.lastname: Saito
authors.forename: Ayako
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Mio
authors.initials: M
authors.lastname: Inoue
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: 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
chemical_list: D024322:Amino Acids, Aromatic; D004220:Disulfides; D008024:Ligands; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D012643:Selenium