Visualization of Ligand-Bound Ectodomain Assembly in the Full-Length Human IGF-1 Receptor by Cryo-EM Single-Particle Analysis
Xi Zhang, Daqi Yu, Jingchuan Sun, Yujie Wu, Junyuan Gong, Xuemei Li, Li Liu, Shan Liu, Jianbo Liu, Yulan Wu, Dongyang Li, Yinping Ma, Xu Han, Yanan Zhu, Zhaolong Wu, Yihua Wang, Qi Ouyang, Tao Wang
Abstract
Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7?? and the IGF-1R/IGF-1 complex at 7.7??. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor.




