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

doi:10.1016/j.str.2020.03.007

Visualization of Ligand-Bound Ectodomain Assembly in the Full-Length Human IGF-1 Receptor by Cryo-EM Single-Particle Analysis

Structure. 2020 May 5;28(5):555-561.e4. doi: 10.1016/j.str.2020.03.007. Epub 2020 Apr 9.

Authors

Xi Zhang¹, Daqi Yu², Jingchuan Sun³, Yujie Wu³, Junyuan Gong⁴, Xuemei Li⁵, Li Liu⁴, Shan Liu⁴, Jianbo Liu³, Yulan Wu⁴, Dongyang Li⁴, Yinping Ma⁶, Xu Han², Yanan Zhu², Zhaolong Wu², Yihua Wang², Qi Ouyang⁷, Tao Wang⁸

Affiliations

¹ School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
² State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China.
³ Institute of Systems Biology, Shenzhen Bay Laboratory, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
⁴ Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
⁵ Electron Microscopy Laboratory, School of Physics, Peking University, Beijing 100871, China.
⁶ Computing Center of Peking University, Peking University, Beijing 100871, China.
⁷ State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, School of Physics, Peking University, Beijing 100871, China; Center for Quantitative Biology, Peking University, Beijing 100871, China.
⁸ Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China; Institute of Systems Biology, Shenzhen Bay Laboratory, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Shenzhen 518109, China. Electronic address: [email protected].

PMID: 32275863
DOI: 10.1016/j.str.2020.03.007

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 Å and the IGF-1R/IGF-1 complex at 7.7 Å. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor.

Keywords: IGF-1; IGF-1r; cryo-EM; insulin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cryoelectron Microscopy
Humans
Insulin / chemistry
Insulin / metabolism
Insulin-Like Growth Factor I / metabolism
Ligands
Models, Molecular
Protein Domains
Receptor, IGF Type 1 / chemistry*
Receptor, IGF Type 1 / metabolism*

Substances

IGF1 protein, human
IGF1R protein, human
Insulin
Ligands
Insulin-Like Growth Factor I
Receptor, IGF Type 1