胰岛素样生长因子-II（IGF-II）如何与人1型胰岛素样生长因子受体结合。

How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor.

作者信息

Xu Yibin, Kirk Nicholas S, Venugopal Hariprasad, Margetts Mai B, Croll Tristan I, Sandow Jarrod J, Webb Andrew I, Delaine Carlie A, Forbes Briony E, Lawrence Michael C

机构信息

Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3050, Australia.

Ramaciotti Centre for Cryo-Electron Microscopy, Monash University, Clayton, VIC 3800, Australia.

出版信息

Structure. 2020 Jul 7;28(7):786-798.e6. doi: 10.1016/j.str.2020.05.002. Epub 2020 May 26.

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.

人类1型胰岛素样生长因子受体（IGF-1R）主要在胰岛素样生长因子I结合时发出信号。尽管胰岛素样生长因子II对IGF-1R的亲和力与胰岛素样生长因子I的亲和力处于同一数量级，但关于胰岛素样生长因子II通过IGF-1R发出信号的作用却知之甚少。在此，我们描述了与亮氨酸拉链稳定的IGF-1R胞外域结合的胰岛素样生长因子II的冷冻电子显微镜结构，该结构以两种构象确定，最大平均分辨率为3.2 Å。这两种构象在它们各自进入膜的点的相对间距上有所不同，并且与结合到IGF-1R的胰岛素样生长因子I的结构进行比较，揭示了长期以来人们所怀疑的各个生长因子的关键C结构域与IGF-1R相互作用方式的差异。