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| Title | Structural basis of the activation of type 1 insulin-like growth factor receptor. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 10, Issue 1, Page 4567, Year 2019 |
| Publish date | Oct 8, 2019 |
 Authors | Jie Li / Eunhee Choi / Hongtao Yu / Xiao-Chen Bai /  |
| PubMed Abstract | Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the ...Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the cryo-EM structure of full-length IGF1R-IGF1 complex in the active state. This structure reveals that only one IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like structure with the unliganded α-CT, which hinders the conformational change of the unliganded α-CT required for binding of a second IGF1 molecule. We further identify an L1-FnIII-2 interaction that mediates the dimerization of membrane-proximal domains of IGF1R. This interaction is required for optimal receptor activation. Our study identifies a source of the negative cooperativity in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation. |
 External links | Nat Commun / PubMed:31594955 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.3 Å |
| Structure data | EMDB-20524, PDB-6pyh: |
| Source |
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 Keywords | SIGNALING PROTEIN/HORMONE / IGF1R / IGF1 / SIGNALING PROTEIN-HORMONE complex |
mus musculus (house mouse)
homo sapiens (human)