Monomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand binding and signaling properties that differ from those of the homodimeric receptors. Here, we describe the cryoelectron microscopy structure of such a hybrid receptor in complex with insulin-like growth factor I (IGF-I). The structure (ca. 3.7 Å resolution) displays a single IGF-I ligand, bound in a similar fashion to that seen for IGFs in complex with IGF-1R. The IGF-I ligand engages the first leucine-rich-repeat domain and cysteine-rich region of the IGF-1R monomer (rather than those of the insulin receptor monomer), consistent with the determinants for IGF binding residing in the IGF-1R cysteine-rich region. The structure broadens our understanding of this receptor family and assists in delineating the key structural motifs involved in binding their respective ligands.

胰岛素受体和 1 型胰岛素样生长因子受体 (IGF-1R) 的单体可以随机结合形成异二聚杂合受体。这些杂合受体表现出与同二聚体受体不同的配体结合和信号传导特性。在这里，我们描述了这种与胰岛素样生长因子 I (IGF-I) 复合的混合受体的低温电子显微镜结构。该结构（约 3.7 Å 分辨率）显示单个 IGF-I 配体，其结合方式与 IGF 与 IGF-1R 复合时所见的方式相似。IGF-I 配体与 IGF-1R 单体（而不是胰岛素受体单体）的第一个富含亮氨酸的重复结构域和富含半胱氨酸的区域接合，这与 IGF-1R 半胱氨酸中的 IGF 结合决定因素一致-丰富的地区。