Cryo-EM structure shows how two IGF1 hormones bind to the human IGF1R receptor

Wu，Cang1,2; Huang，Xin2; Dong，Fengquan3; Tang，Wenfang1; Shi，Jing1; Lu，Xin2; Shu，Qing1; Zhang，Xi1,2,4

2022-12-25

10.1016/j.bbrc.2022.10.056

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Impact Factor & Quartile

0006-291X

1090-2104

IGF1R plays an important role in regulating cellular metabolism and cell growth, and has been identified as an anti-cancer and diabetes drug target. Although research have been reported many crystal and cryo-EM structures of IGF1R, the mechanism of ligand binding remains controversial, mainly because the structure differences among its cryo-EM, crystal and homologous protein insulin receptor structures. Here, we further determined one new high-resolution symmetric cryo-EM structure of ligand-bound IGF1R and be the first to prove that the receptor could bind to two IGFI molecules by single particle cryo-electron microscopy. And the structure is very different from its homologous protein insulin receptor: the two ligands just exist at the binding site 2 with saturating ligand conditions. Then, our findings resolved the major dispute about the comformational changes of IGF1R, and proposed a new theory how IGF1R binds to its ligands. Meanwhile, these findings imply more attention may be needed to study the relationship between the special conformation and their corresponding physiological functions in future.

Cryo-EM IGF1 IGF1R

SCI

English

Corresponding

Guangdong Medical Research Foundation[A2021333];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20190808120613189];

Biochemistry & Molecular Biology ; Biophysics

Biochemistry & Molecular Biology ; Biophysics

WOS:000891622200016

ACADEMIC PRESS INC ELSEVIER SCIENCE

BIOLOGY & BIOCHEMISTRY

2-s2.0-85140605133

Scopus

1.Shenzhen People's Second Hospital & The First Affiliated Hospital of Shenzhen University,Shenzhen,Guangdong,518000,China
2.Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
3.Shenzhen University General Hospital,Shenzhen,Guangdong,518055,China
4.Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,518055,China

Wu，Cang,Huang，Xin,Dong，Fengquan,et al. Cryo-EM structure shows how two IGF1 hormones bind to the human IGF1R receptor[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2022,636:121-124.

Wu，Cang.,Huang，Xin.,Dong，Fengquan.,Tang，Wenfang.,Shi，Jing.,...&Zhang，Xi.(2022).Cryo-EM structure shows how two IGF1 hormones bind to the human IGF1R receptor.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,636,121-124.

Wu，Cang,et al."Cryo-EM structure shows how two IGF1 hormones bind to the human IGF1R receptor".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 636(2022):121-124.