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.

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