Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R.

人1型胰岛素样生长因子受体（IGF-1R）的信号主要是响应于胰岛素样生长因子I的结合。尽管有人知道，通过IGF-1R进行的胰岛素样生长因子II信号的作用知之甚少胰岛素样生长因子II对IGF-1R的亲和力在胰岛素样生长因子I亲和力的数量级之内。在这里，我们描述胰岛素样生长因子II与亮氨酸拉链结合的冷冻电子显微镜结构稳定的IGF-1R胞外域，以两个构象确定，最大平均分辨率为3.2。两种构型在各自的膜进入点的相对分离方面有所不同，