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- PDB-6vwh: Leg region of the open conformation of the human type 1 insulin-l... -
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Basic information
Entry | Database: PDB / ID: 6vwh | |||||||||
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Title | Leg region of the open conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II. | |||||||||
![]() | Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain | |||||||||
![]() | SIGNALING PROTEIN / Type 1 insulin-like growth factor receptor / Insulin-like growth factor II / ectodomain receptor / tyrosine kinase | |||||||||
Function / homology | ![]() cardiac atrium development / negative regulation of cholangiocyte apoptotic process / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / negative regulation of muscle cell apoptotic process ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / protein localization to nuclear periphery / FCERI mediated MAPK activation / cellular response to zinc ion starvation / cellular response to aldosterone / Activation of the AP-1 family of transcription factors / response to amino acid starvation / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / insulin receptor activity / transcytosis / nitrogen catabolite activation of transcription from RNA polymerase II promoter / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / Oxidative Stress Induced Senescence / cellular response to angiotensin / positive regulation of protein-containing complex disassembly / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / response to L-glutamate / insulin binding / negative regulation of MAPK cascade / establishment of cell polarity / positive regulation of axon regeneration / amyloid-beta clearance / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / TFIID-class transcription factor complex binding / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / insulin receptor substrate binding / estrous cycle / G-protein alpha-subunit binding / response to vitamin E / positive regulation of transcription initiation by RNA polymerase II / SHC-related events triggered by IGF1R / positive regulation of RNA polymerase II transcription preinitiation complex assembly / phosphatidylinositol 3-kinase binding / amino acid biosynthetic process / peptidyl-tyrosine autophosphorylation / cellular response to transforming growth factor beta stimulus / T-tubule / cellular response to amino acid starvation / cellular response to dexamethasone stimulus / cerebellum development / axonogenesis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / insulin-like growth factor receptor signaling pathway / caveola / cellular response to estradiol stimulus / hippocampus development / cellular response to glucose stimulus / positive regulation of smooth muscle cell proliferation / response to nicotine / insulin receptor binding / receptor protein-tyrosine kinase / cellular response to mechanical stimulus / RNA polymerase II transcription regulator complex / cellular response to amyloid-beta / : / cellular senescence / insulin receptor signaling pathway / positive regulation of cold-induced thermogenesis / DNA-binding transcription activator activity, RNA polymerase II-specific / protein tyrosine kinase activity / response to ethanol / RNA polymerase II-specific DNA-binding transcription factor binding / sequence-specific DNA binding / transcription regulator complex / positive regulation of MAPK cascade / protein autophosphorylation / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / DNA-binding transcription factor activity, RNA polymerase II-specific / regulation of cell cycle / intracellular signal transduction / positive regulation of cell migration / immune response / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / axon / intracellular membrane-bounded organelle / neuronal cell body Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.26 Å | |||||||||
![]() | Xu, Y. / Kirk, N.S. / Lawrence, M.C. / Croll, T.I. | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor. Authors: Yibin Xu / Nicholas S Kirk / Hariprasad Venugopal / Mai B Margetts / Tristan I Croll / Jarrod J Sandow / Andrew I Webb / Carlie A Delaine / Briony E Forbes / Michael C Lawrence / ![]() ![]() Abstract: Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth ...Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 207.7 KB | Display | ![]() |
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PDB format | ![]() | 162 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 740.1 KB | Display | ![]() |
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Full document | ![]() | 746.4 KB | Display | |
Data in XML | ![]() | 22.9 KB | Display | |
Data in CIF | ![]() | 32.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21416MC ![]() 6vwgC ![]() 6vwiC ![]() 6vwjC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 108937.242 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: IGF1R, GCN4, AAS3, ARG9, YEL009C / Plasmid: pEE14 / Strain: ATCC 204508 / S288c / Cell line (production host): CHO-K1 / Production host: ![]() ![]() References: UniProt: P08069, UniProt: P03069, receptor protein-tyrosine kinase |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: leg region of the open-leg conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II. Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight | Value: 0.25 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: IGFII:IGF-1R molar ratio 1.5:1 | ||||||||||||||||||||
Specimen support | Details: 15mA current / Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil, UltrAuFoil, R1.2/1.3 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 10 sec. / Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 4585 |
EM imaging optics | Energyfilter name: GIF Quantum LS |
Image scans | Movie frames/image: 50 / Used frames/image: 1-50 |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2057701 | |||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.26 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 205471 / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL Details: UCSF Chimera was used for the initial fitting and ISOLDE v 1.03b was using for flexible fitting. | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5U8R | |||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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