Cryo-EM studies of the apo states of human IGF1R

IGF1R plays an important role in regulating cellular metabolism and growth. As a single transmembrane protein, its structure is flexible. Although previous studies revealed some structures of IGF1R, the cryoEM apo structures of the receptor have never been reported. Herein, we reported four distinct cryo-EM structures that reveal the apo states of IGF1R. These conformations were classified as Resting states and Active states, according to the orientation of alpha-CT helices and structural symmetry. In addition, a Ligand-pocket was formed in the active conformations, which presented a new view of conformational changes of apo-IGF1R. These results suggest a new dynamic change model to show the details of why and how ligands can bind to IGF1R. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

IGF1R, a crucial protein in cellular metabolism and growth regulation, exhibits flexible structure as a single transmembrane protein. In this study, four distinct cryo-EM structures of IGF1R in apo states were reported, classified as Resting states and Active states based on the orientation of alpha-CT helices and structural symmetry. The active conformations revealed the formation of a Ligand-pocket, providing new insights into the conformational changes of apo-IGF1R and the binding mechanism of ligands.