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	Mechanism of receptor assembly via the pleiotropic adipokine Leptin.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 30, Issue 4, Page 551-563, Year 2023
Publish date	Mar 23, 2023
Authors	Alexandra Tsirigotaki / Ann Dansercoer / Koen H G Verschueren / Iva Marković / Christoph Pollmann / Maximillian Hafer / Jan Felix / Catherine Birck / Wouter Van Putte / Dominiek Catteeuw / Jan Tavernier / J Fernando Bazan / Jacob Piehler / Savvas N Savvides / Kenneth Verstraete /
PubMed Abstract	The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and cancer. However, the structure and ...The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and cancer. However, the structure and mechanism of Leptin-mediated LEP-R assemblies has remained unclear. Intriguingly, the signaling-competent isoform of LEP-R is only lowly abundant amid several inactive short LEP-R isoforms contributing to a mechanistic conundrum. Here we show by X-ray crystallography and cryo-EM that, in contrast to long-standing paradigms, Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry and demonstrate such Leptin-induced trimerization of LEP-R on living cells via single-molecule microscopy. In mediating these assemblies, Leptin undergoes drastic restructuring that activates its site III for binding to the Ig domain of an adjacent LEP-R. These interactions are abolished by mutations linked to obesity. Collectively, our study provides the structural and mechanistic framework for how evolutionarily conserved Leptin:LEP-R assemblies with 3:3 stoichiometry can engage distinct LEP-R isoforms to achieve signaling.
External links	Nat Struct Mol Biol / PubMed:36959263
Methods	EM (single particle) / X-ray diffraction
Resolution	1.75 - 6.84 Å
Structure data	15677 8avb EMDB-15677: Cryo-EM structure for mouse leptin in complex with the mouse LEP-R ectodomain (1:2 mLEP:mLEPR model) PDB-8avb: Cryo-EM structure for mouse leptin in complex with the mouse LEP-R ectodomain (1:2 mLEP:mLEPR model). Method: EM (single particle) / Resolution: 4.43 Å 15678 8avc EMDB-15678, PDB-8avc: Mouse leptin:LEP-R complex cryoEM structure (3:3 model) Method: EM (single particle) / Resolution: 4.6 Å 15679 8avd EMDB-15679, PDB-8avd: Cryo-EM structure for a 3:3 complex between mouse leptin and the mouse LEP-R ectodomain (local refinement) Method: EM (single particle) / Resolution: 4.42 Å 15680 8ave EMDB-15680, PDB-8ave: Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (2:2 model) Method: EM (single particle) / Resolution: 5.62 Å 15681 8avf EMDB-15681, PDB-8avf: Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (closed 3:3 model) Method: EM (single particle) / Resolution: 6.45 Å 15683 8avo EMDB-15683, PDB-8avo: Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (open 3:3 model). Method: EM (single particle) / Resolution: 6.84 Å 15899 8b7q EMDB-15899, PDB-8b7q: Cryo-EM structure for the mouse LEPR-CRH2:Leptin:LEPR-Ig complex following symmetry expansion in combination with local refinement Method: EM (single particle) / Resolution: 4.02 Å PDB-7z3p: Crystal structure of the mouse leptin:LepR-CRH2 encounter complex to 1.95 A resolution. Method: X-RAY DIFFRACTION / Resolution: 1.943 Å PDB-7z3q: Crystal structure of the human leptin:LepR-CRH2 encounter complex to 3.6 A resolution. Method: X-RAY DIFFRACTION / Resolution: 3.617 Å PDB-7z3r: Crystal structure of the mouse leptin:LepR-IgCRH2 complex to 2.95 A resolution. Method: X-RAY DIFFRACTION / Resolution: 2.951 Å PDB-8av2: Crystal structure for the FnIII module of mouse LEP-R in complex with the anti-LEP-R nanobody VHH-4.80 Method: X-RAY DIFFRACTION / Resolution: 1.75 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-PEG: DI(HYDROXYETHYL)ETHER / Diethylene glycol ChemComp-HOH: WATER / Water ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-SO4: SULFATE ION / Sulfate ChemComp-NI: NICKEL (II) ION / Nickel
Source	mus musculus (house mouse) homo sapiens (human) lama glama (llama)
Keywords	CYTOKINE / leptin / obesity / leptin receptor / LepR / adipose tissue / hypothalamus / immune system / LEP-R / metabolism / energy balance