Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor
Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor
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作者：
Garrett, TPJ;McKern, NM;Ward, CW
1型胰岛素样生长因子受体（IGF-1 R）和胰岛素受体（IR）是酪氨酸激酶受体超家族的密切相关成员。IR是葡萄糖稳态所必需的，而IGF-1 R参与正常生长发育和恶性转化。在像刺胞动物这样简单的动物中发现了这些受体的同源物。表皮生长因子受体（EGFR）家族与IR家族密切相关，并且与我们在此描述的细胞外部分具有显著的序列同一性。我们现在呈现了IGF-1 R的前三个结构域（L1-Cys-rich-L2）的结构，其确定为2.4埃分辨率。L结构域各自由单链右手β-螺旋组成。富含Cys的区域由八个二硫键键合的模块组成，其中七个模块以不寻常的方式与模块形成棒状结构域。这三个结构域围绕着一个足够大的中心空间，以容纳配体分子。尽管该片段（残基1-462）不结合配体，但许多负责激素结合和配体特异性的决定簇映射到该中心位点。因此，该结构显示了IR亚家族如何与其配体相互作用。
The type-1 insulin-like growth-factor receptor (IGF-1R) and insulin receptor (IR) are closely related members of the tyrosine-kinase receptor superfamily. IR is essential for glucose homeostasis, whereas IGF-1R is involved in both normal growth and development and malignant transformation. Homologues of these receptors are found in animals as simple as cnidarians. The epidermal growth-factor receptor (EGFR) family is closely related to the IR family and has significant sequence identity to the extracellular portion we describe here. We now present the structure of the first three domains of IGF-1R (L1-Cys-rich-L2) determined to a 2.4 Angstrom resolution. The L domains each consist of a single-stranded right-handed beta-helix. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain with modules associated in an unusual manner. The three domains surround a central space of sufficient size to accommodate a ligand molecule. Although the fragment (residues 1-462) does not bind ligand, many of the determinants responsible for hormone binding and ligand specificity map to this central site. This structure therefore shows how the IR subfamily might interact with their ligands.