Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor α
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor α
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DOI：
10.1016/s0092-8674(02)00940-6
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发表时间：
2002-09-20
期刊：
影响因子：
64.5
通讯作者：
Ward, CW
中科院分区：
文献类型：
--
作者：
Garrett, TPJ;McKern, NM;Ward, CW
我们报告的晶体结构，在2.5埃分辨率，截短的人EGFR胞外域结合TGF α。TGF α与EGFR的L1和L2结构域相互作用，使许多主链与L1接触，并通过关键保守残基与L2相互作用。结果表明EGFR家族成员如何结合高度可变的配体家族。在2：2 TGF α：sEGFR 501复合物中，每个配体仅与一个受体分子相互作用。存在两种类型的二聚体;在不对称单元中：涉及L1和L2结构域之间的接触的头对头二聚体和由每个受体的CRI结构域之间的相互作用主导的背对背二聚体。基于序列保守性、埋藏表面积和诱变实验，背靠背二聚体有利于生物学相关。
We report the crystal structure, at 2.5 Angstrom resolution, of a truncated human EGFR ectodomain bound to TGFalpha. TGFalpha interacts with both L1 and L2 domains of EGFR, making many main chain contacts with L1 and interacting with L2 via key conserved residues. The results indicate how EGFR family members can bind a family of highly variable ligands. In the 2:2 TGFalpha:sEGFR501 complex, each ligand interacts with only one receptor molecule. There are two types of dimers; in the asymmetric unit: a head-to-head dimer involving contacts between the L1 and L2 domains and a back-to-back dimer dominated by interactions between the CRI domains of each receptor. Based on sequence conservation, buried surface area, and mutagenesis experiments, the back-to-back dimer is favored to be biologically relevant.