6PYH

Cryo-EM structure of full-length IGF1R-IGF1 complex. Only the extracellular region of the complex is resolved.

Summary for 6PYH

• Entry DOI: 10.2210/pdb6pyh/pdb
• EMDB information: 20524
• Descriptor: Insulin-like growth factor 1 receptor, Insulin-like growth factor I (2 entities in total)
• Functional Keywords: igf1r, igf1, signaling protein-hormone complex, signaling protein/hormone
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 298223.56

Authors

Li, J.,Choi, E.,Yu, H.T.,Bai, X.C. (deposition date: 2019-07-29, release date: 2019-10-23, Last modification date: 2024-10-30)

Primary citation

Li, J.,Choi, E.,Yu, H.,Bai, X.C.
Structural basis of the activation of type 1 insulin-like growth factor receptor.
Nat Commun, 10:4567-4567, 2019

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 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.

PubMed: 31594955
DOI: 10.1038/s41467-019-12564-0

Experimental method

ELECTRON MICROSCOPY (4.3 Å)