Cryo-EM studies of the apo states of human IGF1R

Xi Zhang; Cang Wu; Tianzi Wei; Yi Lu; Chuang Liu; Jian Zhang

doi:10.1016/j.bbrc.2022.05.063

Cryo-EM studies of the apo states of human IGF1R

Biochem Biophys Res Commun. 2022 Aug 27:618:148-152. doi: 10.1016/j.bbrc.2022.05.063. Epub 2022 May 20.

Authors

Xi Zhang¹, Cang Wu², Tianzi Wei³, Yi Lu⁴, Chuang Liu⁵, Jian Zhang⁶

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, Shenzhen People's Second Hospital, Shenzhen, 518000, Guangdong, China; Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China; Cryo-EM Centre, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
² Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
³ Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, Hong Kong SAR, China.
⁴ School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. Electronic address: luy3@sustech.edu.cn.
⁵ Centre for PanorOmic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, Hong Kong SAR, China. Electronic address: Liuc7@hku.hk.
⁶ School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. Electronic address: zhangjian@sustech.ed.

PMID: 35749888
DOI: 10.1016/j.bbrc.2022.05.063

Abstract

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 cryo-EM 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 α-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.

Keywords: Apo-IGF1R; Conformation change; Cryo-EM.

Publication types

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

MeSH terms

Cryoelectron Microscopy / methods
Humans
Ligands
Protein Conformation
Receptor, IGF Type 1* / chemistry
Receptor, IGF Type 1* / ultrastructure

Substances

IGF1R protein, human
Ligands
Receptor, IGF Type 1