Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor.
Journal, issue, pages	Elife, Vol. 11, Year 2022
Publish date	Nov 22, 2022
Authors	Jie Li / Jiayi Wu / Catherine Hall / Xiao-Chen Bai / Eunhee Choi /
PubMed Abstract	The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked ...The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked homodimers in the apo-state; however, their ligand binding properties and the structures in the active state differ substantially. It has been proposed that the disulfide-linked C-terminal segment of α-chain (αCTs) of the IR and IGF1R control the cooperativity of ligand binding and regulate the receptor activation. Nevertheless, the molecular basis for the roles of disulfide-linked αCTs in IR and IGF1R activation are still unclear. Here, we report the cryo-EM structures of full-length mouse IGF1R/IGF1 and IR/insulin complexes with modified αCTs that have increased flexibility. Unlike the -shaped asymmetric IGF1R dimer with a single IGF1 bound, the IGF1R with the enhanced flexibility of αCTs can form a -shaped symmetric dimer with two IGF1s bound. Meanwhile, the IR with non-covalently linked αCTs predominantly adopts an asymmetric conformation with four insulins bound, which is distinct from the -shaped symmetric IR. Using cell-based experiments, we further showed that both IGF1R and IR with the modified αCTs cannot activate the downstream signaling potently. Collectively, our studies demonstrate that the certain structural rigidity of disulfide-linked αCTs is critical for optimal IR and IGF1R signaling activation.
External links	Elife / PubMed:36413010 / PubMed Central
Methods	EM (single particle)
Resolution	3.7 - 4.9 Å
Structure data	28693 8eyr EMDB-28693, PDB-8eyr: Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation Method: EM (single particle) / Resolution: 4.0 Å 28723 8eyx EMDB-28723: Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically decoupled alpha CTs (C684S/C685S/C687S, denoted as IR-3CS) Asymmetric conformation 1 PDB-8eyx: Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically decoupled alpha CTs (C684S/C685S/C687S; denoted as IR-3CS) Asymmetric conformation 1 Method: EM (single particle) / Resolution: 4.5 Å 28724 8eyy EMDB-28724, PDB-8eyy: Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically decoupled alpha CTs (C684S/C685S/C687S, denoted as IR-3CS) Asymmetric conformation 2 Method: EM (single particle) / Resolution: 4.9 Å 28725 8ez0 EMDB-28725, PDB-8ez0: Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically decoupled alpha CTs (C684S/C685S/C687S; denoted as IR-3CS) Symmetric conformation Method: EM (single particle) / Resolution: 3.7 Å
Source	mus musculus (house mouse) homo sapiens (human)
Keywords	SIGNALING PROTEIN / IGF1R / IGF1 / Insulin receptor / insulin