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- PDB-7v3p: Cryo-EM structure of the IGF1R/insulin complex -

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Basic information

Entry
Database: PDB / ID: 7v3p
TitleCryo-EM structure of the IGF1R/insulin complex
Components
  • Insulin A chain
  • Insulin B chain
  • Insulin-like growth factor 1 receptor
KeywordsMEMBRANE PROTEIN / The type 1 insulin-like growth factor receptor (IGF1R)
Function / homology
Function and homology information


cardiac atrium development / negative regulation of cholangiocyte apoptotic process / positive regulation of steroid hormone biosynthetic process / protein kinase complex / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / positive regulation of steroid hormone biosynthetic process / protein kinase complex / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / cellular response to zinc ion starvation / cellular response to aldosterone / cellular response to testosterone stimulus / insulin receptor complex / transcytosis / insulin-like growth factor I binding / negative regulation of hepatocyte apoptotic process / positive regulation of protein-containing complex disassembly / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / regulation of JNK cascade / dendritic spine maintenance / insulin binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / cellular response to insulin-like growth factor stimulus / response to L-glutamate / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / Signaling by Insulin receptor / negative regulation of feeding behavior / IRS activation / Insulin processing / regulation of protein secretion / establishment of cell polarity / positive regulation of axon regeneration / positive regulation of peptide hormone secretion / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / positive regulation of respiratory burst / amyloid-beta clearance / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / positive regulation of protein autophosphorylation / Respiratory syncytial virus (RSV) attachment and entry / alpha-beta T cell activation / insulin receptor substrate binding / cellular response to angiotensin / positive regulation of dendritic spine maintenance / response to vitamin E / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of respiratory burst involved in inflammatory response / G-protein alpha-subunit binding / negative regulation of protein secretion / negative regulation of MAPK cascade / negative regulation of gluconeogenesis / positive regulation of glycogen biosynthetic process / Signal attenuation / fatty acid homeostasis / SHC-related events triggered by IGF1R / phosphatidylinositol 3-kinase binding / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / positive regulation of insulin receptor signaling pathway / negative regulation of lipid catabolic process / regulation of protein localization to plasma membrane / positive regulation of lipid biosynthetic process / peptidyl-tyrosine autophosphorylation / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / activation of protein kinase B activity / COPI-mediated anterograde transport / estrous cycle / transport vesicle / nitric oxide-cGMP-mediated signaling / cellular response to transforming growth factor beta stimulus / negative regulation of reactive oxygen species biosynthetic process / Insulin receptor recycling / insulin-like growth factor receptor binding / positive regulation of brown fat cell differentiation / NPAS4 regulates expression of target genes / T-tubule / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of nitric-oxide synthase activity / positive regulation of mitotic nuclear division / cerebellum development / Insulin receptor signalling cascade / cellular response to dexamethasone stimulus / regulation of transmembrane transporter activity / axonogenesis / insulin-like growth factor receptor signaling pathway / hippocampus development / positive regulation of glycolytic process / positive regulation of long-term synaptic potentiation / positive regulation of cytokine production / endosome lumen / acute-phase response / positive regulation of D-glucose import / positive regulation of protein secretion / positive regulation of cell differentiation
Similarity search - Function
Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A domain 2 / Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A, domain 2 / 24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Alpha-Beta Horseshoe / Insulin / Insulin family ...Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A domain 2 / Hormone Receptor, Insulin-like Growth Factor Receptor 1; Chain A, domain 2 / 24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Alpha-Beta Horseshoe / Insulin / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / : / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Ribbon / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Insulin / Insulin-like growth factor 1 receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsZhang, J. / Liu, C. / Zhang, X. / Wei, T. / Wu, C.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81972766 China
CitationJournal: To Be Published
Title: Cryo-EM structure of the IGF1R/insulin complex
Authors: Liu, C. / Zhang, J. / Zhang, X. / Wei, T. / Wu, C.
History
DepositionAug 11, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 17, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_entry_details / pdbx_modification_feature
Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Insulin-like growth factor 1 receptor
B: Insulin-like growth factor 1 receptor
E: Insulin A chain
F: Insulin B chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)218,3528
Polymers217,4674
Non-polymers8854
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area10840 Å2
ΔGint-40 kcal/mol
Surface area86290 Å2

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Components

#1: Protein Insulin-like growth factor 1 receptor / Insulin-like growth factor I receptor / IGF-I receptor


Mass: 105824.719 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IGF1R / Production host: Homo sapiens (human)
References: UniProt: P08069, receptor protein-tyrosine kinase
#2: Protein/peptide Insulin A chain / Small chain


Mass: 2383.698 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INS / Production host: Homo sapiens (human) / References: UniProt: P01308
#3: Protein/peptide Insulin B chain / Large chain


Mass: 3433.953 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INS / Production host: Homo sapiens (human) / References: UniProt: P01308
#4: 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.: 4 / 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: Complex of the dimer IGF1R with insulin / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenConc.: 1.5 mg/ml / Embedding 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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 356200 / Symmetry type: POINT

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