Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains
Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains
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DOI：
10.1016/s0092-8674(02)00963-7
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发表时间：
2002-09-20
期刊：
影响因子：
64.5
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Ogiso, H;Ishitani, R;Yokoyama, S
表皮生长因子（EGF）通过与包含结构域I-IV的EGF受体（EGFR）胞外区结合，产生受体酪氨酸激酶的二聚化来调节细胞增殖和分化。在这项研究中，人EGF和EGFR胞外区的2：2复合物的晶体结构已被确定在3.3埃分辨率。EGFR结构域I-III以C形排列，EGF对接在结构域I和III之间。1：1的EGF·EGFR复合物通过直接的受体-受体相互作用而二聚化，其中每个结构域II的突出的β-发夹臂保持另一个结构域的主体。通过EGFR诱变验证了独特的“受体介导的二聚化”。
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.