WEHI, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3050, Australia.
WEHI, 1G Royal Parade, Parkville, VIC 3052, Australia.
Structure. 2022 Aug 4;30(8):1098-1108.e6. doi: 10.1016/j.str.2022.05.007. Epub 2022 Jun 3.
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体杂合受体。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转导特性。在这里，我们描述了与胰岛素样生长因子 I (IGF-I) 结合的这种杂合受体的冷冻电镜结构。该结构（约 3.7Å 分辨率）显示了一个单独的 IGF-I 配体，以与 IGFs 与 IGF-1R 结合时相似的方式结合。IGF-I 配体与 IGF-1R 单体的第一个富含亮氨酸重复结构域和富含半胱氨酸区域结合（而不是胰岛素受体单体的结合），这与 IGF 结合的决定因素位于 IGF-1R 富含半胱氨酸区域一致。该结构拓宽了我们对该受体家族的理解，并有助于描绘与其各自配体结合相关的关键结构模体。
