Cryo-EM Structure Reveals Polymorphic Ligand-bound States of IGF1R. Issue 9 (15th May 2022)
- Record Type:
- Journal Article
- Title:
- Cryo-EM Structure Reveals Polymorphic Ligand-bound States of IGF1R. Issue 9 (15th May 2022)
- Main Title:
- Cryo-EM Structure Reveals Polymorphic Ligand-bound States of IGF1R
- Authors:
- Zhang, Xi
Wei, Tianzi
Wu, Cang
Jiang, Junyi
Chen, Shengming
Hu, Yinqing
Lu, Yi
Sun, Dayong
Zhai, Liting
Zhang, Jian
Liu, Chuang - Abstract:
- Graphical abstract: Highlights: Cryo–EM structures show the polymorphic ligand-bound states of IGF1R. The orientation of α-CT 2, disulfide bond (C670-C670′) and FnIII-2 domains was the most flexible parts for the conformation change when ligand binds to the receptor. These results illustrated the mechanism of how different ligands could bind to human IGF1R, and provided a rational template for drug design. Abstract: Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in regulating cellular metabolism and cell growth and has been identified as an anticancer drug target. Although previous studies have revealed some structures of IGF1R with different ligands, the continuous dynamic conformation change remains unclear. Here, we report 10 distinct structures (7.9–3.6 Å) of IGF1R bound to IGF1 or insulin to reveal the polymorphic conformations of ligand-bound IGF1R. These results showed that the α-CT 2, disulfide bond (C670-C670′), and FnIII-2 domains had the most flexible orientations for the conformational change that occurs when ligands bind to the receptor. In addition, we found one special conformation (tentatively named the diverter-switch state) in both complexes, which may be one of the apo-IGF1R forms under ligand-treatment conditions. Hence, these results illustrated the mechanism of how different ligands could bind to human IGF1R and provided a rational template for drug design.
- Is Part Of:
- Journal of molecular biology. Volume 434:Issue 9(2022)
- Journal:
- Journal of molecular biology
- Issue:
- Volume 434:Issue 9(2022)
- Issue Display:
- Volume 434, Issue 9 (2022)
- Year:
- 2022
- Volume:
- 434
- Issue:
- 9
- Issue Sort Value:
- 2022-0434-0009-0000
- Page Start:
- Page End:
- Publication Date:
- 2022-05-15
- Subjects:
- IGF1R -- IGF1 -- insulin -- ligand-bound states -- conformation change
Molecular biology -- Periodicals
Biology -- Periodicals
Biochemistry -- Periodicals
Bacteriology -- Periodicals
Molecular Biology -- Periodicals
Biochemistry -- Periodicals
Biologie moléculaire -- Périodiques
Biologie -- Périodiques
Biochimie -- Périodiques
Moleculaire biologie
Biochemistry
Biology
Molecular biology
Periodicals
572.805 - Journal URLs:
- http://www.sciencedirect.com/science/journal/00222836 ↗
http://www.elsevier.com/journals ↗ - DOI:
- 10.1016/j.jmb.2022.167536 ↗
- Languages:
- English
- ISSNs:
- 0022-2836
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 5020.700000
British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 21411.xml