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
Author
Journal
IF	>30 >20 >10 >5 all

Title	Synergistic activation of the insulin receptor via two distinct sites.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 29, Issue 4, Page 357-368, Year 2022
Publish date	Mar 31, 2022
Authors	Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai /
PubMed Abstract	Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ...Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation.
External links	Nat Struct Mol Biol / PubMed:35361965 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 5.0 Å
Structure data	25188 7sl1 EMDB-25188, PDB-7sl1: Full-length insulin receptor bound with site 1 binding deficient mutant insulin (A-V3E) Method: EM (single particle) / Resolution: 3.4 Å 25189 7sl2 EMDB-25189, PDB-7sl2: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R) -- asymmetric conformation Method: EM (single particle) / Resolution: 3.6 Å 25190 7sl3 EMDB-25190, PDB-7sl3: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R) -- symmetric conformation Method: EM (single particle) / Resolution: 3.4 Å 25191 7sl4 EMDB-25191, PDB-7sl4: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R) -- asymmetric conformation Method: EM (single particle) / Resolution: 5.0 Å 25192 7sl6 EMDB-25192, PDB-7sl6: Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R) -- symmetric conformation Method: EM (single particle) / Resolution: 3.7 Å 25193 7sl7 EMDB-25193, PDB-7sl7: Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R) Method: EM (single particle) / Resolution: 3.1 Å 25428 7sth EMDB-25428, PDB-7sth: Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound) symmetric conformation Method: EM (single particle) / Resolution: 3.5 Å 25429 7sti EMDB-25429, PDB-7sti: Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation Method: EM (single particle) / Resolution: 4.9 Å 25430 7stj EMDB-25430, PDB-7stj: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 1) Method: EM (single particle) / Resolution: 4.4 Å 25431 7stk EMDB-25431, PDB-7stk: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) Method: EM (single particle) / Resolution: 4.0 Å
Source	mus musculus (house mouse) homo sapiens (human)
Keywords	SIGNALING PROTEIN/HORMONE / insulin receptor / site 1 binding deficient mutant insulin / SIGNALING PROTEIN / SIGNALING PROTEIN-HORMONE complex / site 2 binding deficient mutant insulin