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- PDB-8x85: Structure of leptin-LepR dimer -

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Basic information

Entry
Database: PDB / ID: 8x85
TitleStructure of leptin-LepR dimer
Components
  • Leptin
  • Leptin receptor
KeywordsCYTOKINE / cytokine receptor / tetramer
Function / homology
Function and homology information


multicellular organism development / leptin receptor activity / regulation of lipoprotein lipid oxidation / cellular response to L-ascorbic acid / positive regulation of fat cell apoptotic process / negative regulation of glutamine transport / activation of protein kinase C activity / negative regulation of appetite by leptin-mediated signaling pathway / positive regulation of luteinizing hormone secretion / negative regulation of glucagon secretion ...multicellular organism development / leptin receptor activity / regulation of lipoprotein lipid oxidation / cellular response to L-ascorbic acid / positive regulation of fat cell apoptotic process / negative regulation of glutamine transport / activation of protein kinase C activity / negative regulation of appetite by leptin-mediated signaling pathway / positive regulation of luteinizing hormone secretion / negative regulation of glucagon secretion / negative regulation of cartilage development / leptin receptor binding / sexual reproduction / regulation of natural killer cell mediated cytotoxicity / regulation of bone remodeling / regulation of endothelial cell proliferation / regulation of natural killer cell proliferation / positive regulation of follicle-stimulating hormone secretion / glycerol biosynthetic process / leptin-mediated signaling pathway / ovulation from ovarian follicle / regulation of transport / regulation of brown fat cell differentiation / bone growth / positive regulation of monoatomic ion transport / energy reserve metabolic process / positive regulation of hepatic stellate cell activation / positive regulation of peroxisome proliferator activated receptor signaling pathway / regulation of nitric-oxide synthase activity / regulation of feeding behavior / adult feeding behavior / bone mineralization involved in bone maturation / regulation of natural killer cell activation / response to leptin / fatty acid catabolic process / negative regulation of D-glucose import across plasma membrane / negative regulation of appetite / positive regulation of developmental growth / prostaglandin secretion / leukocyte tethering or rolling / cellular response to leptin stimulus / cardiac muscle hypertrophy / intestinal absorption / Signaling by Leptin / positive regulation of p38MAPK cascade / cell surface receptor signaling pathway via STAT / cytokine receptor activity / response to dietary excess / negative regulation of vasoconstriction / response to vitamin E / peptide hormone receptor binding / regulation of cytokine production involved in inflammatory response / cytokine binding / peptide hormone binding / T cell differentiation / negative regulation of lipid storage / Synthesis, secretion, and deacylation of Ghrelin / regulation of angiogenesis / positive regulation of insulin receptor signaling pathway / positive regulation of TOR signaling / energy homeostasis / positive regulation of interleukin-12 production / cellular response to retinoic acid / phagocytosis / cell surface receptor signaling pathway via JAK-STAT / transport across blood-brain barrier / positive regulation of T cell proliferation / placenta development / negative regulation of autophagy / response to activity / positive regulation of interleukin-8 production / lipid metabolic process / positive regulation of receptor signaling pathway via JAK-STAT / female pregnancy / circadian rhythm / response to insulin / hormone activity / Transcriptional regulation of white adipocyte differentiation / positive regulation of protein import into nucleus / positive regulation of interleukin-6 production / regulation of blood pressure / positive regulation of reactive oxygen species metabolic process / cytokine-mediated signaling pathway / glucose homeostasis / positive regulation of tumor necrosis factor production / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / response to estradiol / transmembrane signaling receptor activity / positive regulation of cold-induced thermogenesis / angiogenesis / response to ethanol / basolateral plasma membrane / response to hypoxia / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cell cycle / signaling receptor complex / cell surface receptor signaling pathway / intracellular signal transduction / external side of plasma membrane
Similarity search - Function
Leptin / Leptin receptor, immunoglobulin-like domain / Leptin / Obesity receptor immunoglobulin like domain / Short hematopoietin receptor, family 1, conserved site / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / Four-helical cytokine-like, core ...Leptin / Leptin receptor, immunoglobulin-like domain / Leptin / Obesity receptor immunoglobulin like domain / Short hematopoietin receptor, family 1, conserved site / Immunoglobulin C2-set-like, ligand-binding / Ig-like C2-type domain / Long hematopoietin receptor, Gp130 family 2, conserved site / Long hematopoietin receptor, gp130 family signature. / Four-helical cytokine-like, core / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like fold
Similarity search - Domain/homology
Leptin / Leptin receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsXie, Y.F. / Shang, G.J. / Qi, J.X. / Gao, G.F.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Hlife / Year: 2023
Title: Structural plasticity of human leptin binding to its receptor LepR
Authors: Xie, Y.F. / Li, X. / Qi, J. / Shang, G. / Lu, D. / Gao, G.F.
History
DepositionNov 27, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 7, 2024Provider: repository / Type: Initial release
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Revision 1.1Nov 13, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.2Nov 27, 2024Group: Data collection / Category: em_admin / Item: _em_admin.last_update
Revision 1.3Jul 2, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Leptin receptor
B: Leptin receptor
C: Leptin
D: Leptin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)230,71317
Polymers227,1804
Non-polymers3,53313
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Leptin receptor / LEP-R / HuB219 / OB receptor / OB-R


Mass: 94933.570 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LEPR, DB, OBR / Production host: Homo sapiens (human) / References: UniProt: P48357
#2: Protein Leptin


Mass: 18656.500 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LEP / Production host: Homo sapiens (human) / References: UniProt: P41159
#3: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 732.682 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/3,4,3/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1221m-1a_1-5]/1-1-2-3/a4-b1_a6-d1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#4: Polysaccharide alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
LFucpa1-6DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-2/a6-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#5: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 11 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Leptin-LepR complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 115281 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00414857
ELECTRON MICROSCOPYf_angle_d0.73320234
ELECTRON MICROSCOPYf_dihedral_angle_d13.0925472
ELECTRON MICROSCOPYf_chiral_restr0.0472343
ELECTRON MICROSCOPYf_plane_restr0.0052507

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