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Yorodumi- EMDB-9838: Cryo-EM structure of the full-length human IGF-1R in complex with... -
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-Basic information
Entry | Database: EMDB / ID: EMD-9838 | ||||||||||||
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Title | Cryo-EM structure of the full-length human IGF-1R in complex with insulin | ||||||||||||
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Sample |
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Keywords | human type 1 insulin-like growth factor receptor / insulin / SIGNALING PROTEIN | ||||||||||||
Function / homology | Function and homology information cardiac atrium development / negative regulation of cholangiocyte apoptotic process / protein kinase complex / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / insulin-like growth factor binding / protein transporter activity / IRS-related events triggered by IGF1R / negative regulation of muscle cell apoptotic process ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / protein kinase complex / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / insulin-like growth factor binding / 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 aldosterone / cellular response to zinc ion starvation / insulin receptor complex / cellular response to testosterone stimulus / insulin-like growth factor I binding / transcytosis / insulin receptor activity / negative regulation of hepatocyte apoptotic process / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / cellular response to angiotensin / positive regulation of protein-containing complex disassembly / dendritic spine maintenance / insulin binding / response to L-glutamate / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / cellular response to insulin-like growth factor stimulus / negative regulation of feeding behavior / establishment of cell polarity / Signaling by Insulin receptor / IRS activation / Insulin processing / regulation of protein secretion / positive regulation of axon regeneration / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / positive regulation of cytokinesis / positive regulation of osteoblast proliferation / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / alpha-beta T cell activation / amyloid-beta clearance / regulation of JNK cascade / Respiratory syncytial virus (RSV) attachment and entry / regulation of amino acid metabolic process / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / Synthesis, secretion, and deacylation of Ghrelin / response to vitamin E / negative regulation of protein secretion / estrous cycle / regulation of protein localization to plasma membrane / fatty acid homeostasis / negative regulation of MAPK cascade / SHC-related events triggered by IGF1R / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / COPI-mediated anterograde transport / phosphatidylinositol 3-kinase binding / positive regulation of lipid biosynthetic process / peptidyl-tyrosine autophosphorylation / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / negative regulation of reactive oxygen species biosynthetic process / transport vesicle / positive regulation of protein autophosphorylation / cellular response to transforming growth factor beta stimulus / Insulin receptor recycling / insulin-like growth factor receptor binding / neuron projection maintenance / T-tubule / positive regulation of protein metabolic process / NPAS4 regulates expression of target genes / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of glycolytic process / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / cellular response to dexamethasone stimulus / cerebellum development / axonogenesis / insulin-like growth factor receptor signaling pathway / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / acute-phase response / cellular response to estradiol stimulus Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.0 Å | ||||||||||||
Authors | Zhang X / Yu D | ||||||||||||
Funding support | China, 3 items
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Citation | Journal: Structure / Year: 2020 Title: Visualization of Ligand-Bound Ectodomain Assembly in the Full-Length Human IGF-1 Receptor by Cryo-EM Single-Particle Analysis. Authors: Xi Zhang / Daqi Yu / Jingchuan Sun / Yujie Wu / Junyuan Gong / Xuemei Li / Li Liu / Shan Liu / Jianbo Liu / Yulan Wu / Dongyang Li / Yinping Ma / Xu Han / Yanan Zhu / Zhaolong Wu / Yihua ...Authors: Xi Zhang / Daqi Yu / Jingchuan Sun / Yujie Wu / Junyuan Gong / Xuemei Li / Li Liu / Shan Liu / Jianbo Liu / Yulan Wu / Dongyang Li / Yinping Ma / Xu Han / Yanan Zhu / Zhaolong Wu / Yihua Wang / Qi Ouyang / Tao Wang / Abstract: Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell ...Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7 Å and the IGF-1R/IGF-1 complex at 7.7 Å. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9838.map.gz | 1.9 MB | EMDB map data format | |
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Header (meta data) | emd-9838-v30.xml emd-9838.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9838_fsc.xml | 5.8 KB | Display | FSC data file |
Images | emd_9838.png | 160.3 KB | ||
Filedesc metadata | emd-9838.cif.gz | 6.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9838 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9838 | HTTPS FTP |
-Validation report
Summary document | emd_9838_validation.pdf.gz | 405 KB | Display | EMDB validaton report |
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Full document | emd_9838_full_validation.pdf.gz | 404.6 KB | Display | |
Data in XML | emd_9838_validation.xml.gz | 8.5 KB | Display | |
Data in CIF | emd_9838_validation.cif.gz | 11 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9838 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9838 | HTTPS FTP |
-Related structure data
Related structure data | 6jk8MC 0741C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9838.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.37 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : complex of full-length human type 1 insulin-like growth factor re...
Entire | Name: complex of full-length human type 1 insulin-like growth factor receptor with insulin |
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Components |
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-Supramolecule #1: complex of full-length human type 1 insulin-like growth factor re...
Supramolecule | Name: complex of full-length human type 1 insulin-like growth factor receptor with insulin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 310 KDa |
-Macromolecule #1: Insulin-like growth factor 1 receptor
Macromolecule | Name: Insulin-like growth factor 1 receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 154.964469 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFR VAGLESLGDL FPNLTVIRGW KLFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL I LDAVSNNY ...String: MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFR VAGLESLGDL FPNLTVIRGW KLFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL I LDAVSNNY IVGNKPPKEC GDLCPGTMEE KPMCEKTTIN NEYNYRCWTT NRCQKMCPST CGKRACTENN ECCHPECLGS CS APDNDTA CVACRHYYYA GVCVPACPPN TYRFEGWRCV DRDFCANILS AESSDSEGFV IHDGECMQEC PSGFIRNGSQ SMY CIPCEG PCPKVCEEEK KTKTIDSVTS AQMLQGCTIF KGNLLINIRR GNNIASELEN FMGLIEVVTG YVKIRHSHAL VSLS FLKNL RLILGEEQLE GNYSFYVLDN QNLQQLWDWD HRNLTIKAGK MYFAFNPKLC VSEIYRMEEV TGTKGRQSKG DINTR NNGE RASCESDVLH FTSTTTSKNR IIITWHRYRP PDYRDLISFT VYYKEAPFKN VTEYDGQDAC GSNSWNMVDV DLPPNK DVE PGILLHGLKP WTQYAVYVKA VTLTMVENDH IRGAKSEILY IRTNASVPSI PLDVLSASNS SSQLIVKWNP PSLPNGN LS YYIVRWQRQP QDGYLYRHNY CSKDKIPIRK YADGTIDIEE VTENPKTEVC GGEKGPCCAC PKTEAEKQAE KEEAEYRK V FENFLHNSIF VPRPERKRRD VMQVANTTMS SRSRNTTAAD TYNITDPEEL ETEYPFFESR VDNKERTVIS NLRPFTLYR IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYG GAKLNRLNPG NYTARIQATS LSGNGSWTDP VFFYVQAKTG YENFIHLIIA LPVAVLLIVG GLVIMLYVFH R KRNNSRLG NGVLYASVNP EYFSAADVYV PDEWEVAREK ITMSRELGQG SFGMVYEGVA KGVVKDEPET RVAIKTVNEA AS MRERIEF LNEASVMKEF NCHHVVRLLG VVSQGQPTLV IMELMTRGDL KSYLRSLRPE MENNPVLAPP SLSKMIQMAG EIA DGMAYL NANKFVHRDL AARNCMVAED FTVKIGDFGM TRDIYETDYY RKGGKGLLPV RWMSPESLKD GVFTTYSDVW SFGV VLWEI ATLAEQPYQG LSNEQVLRFV MEGGLLDKPD NCPDMLFELM RMCWQYNPKM RPSFLEIISS IKEEMEPGFR EVSFY YSEE NKLPEPEELD LEPENMESVP LDPSASSSSL PLPDRHSGHK AENGPGPGVL VLRASFDERQ PYAHMNGGRK NERALP LPQ SSTC UniProtKB: Insulin-like growth factor 1 receptor |
-Macromolecule #2: Insulin
Macromolecule | Name: Insulin / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.989862 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED LQVGQVELGG GPGAGSLQPL ALEGSLQKR GIVEQCCTSI CSLYQLENYC N UniProtKB: Insulin |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.4 / Details: PBS with detergent |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
Details | human type 1 insulin-like growth factor receptor saturated with human insulin |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 36496 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 105000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |