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- EMDB-24927: Leg region of a complex of IGF-I with the ectodomain of a hybrid ... -
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Basic information
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Title | Leg region of a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor | |||||||||
![]() | Leg region of IGF1R/INSR | |||||||||
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![]() | Insulin receptor / Type 1 insulin like growth factor receptor / hybrid receptor / insulin like growth factor I / leucine zipper / cryo electron microscopy / SIGNALING PROTEIN | |||||||||
Function / homology | ![]() cardiac atrium development / negative regulation of cholangiocyte apoptotic process / positive regulation of steroid hormone biosynthetic process / protein kinase complex / protein transporter activity / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / 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 / protein transporter activity / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / regulation of female gonad development / positive regulation of meiotic cell cycle / cellular response to zinc ion starvation / cellular response to aldosterone / insulin-like growth factor II binding / positive regulation of developmental growth / male sex determination / cellular response to testosterone stimulus / insulin receptor complex / exocrine pancreas development / insulin-like growth factor I binding / transcytosis / negative regulation of hepatocyte apoptotic process / positive regulation of protein-containing complex disassembly / regulation of JNK cascade / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / dendritic spine maintenance / cargo receptor activity / insulin binding / PTB domain binding / adrenal gland development / neuronal cell body membrane / response to L-glutamate / cellular response to insulin-like growth factor stimulus / Signaling by Insulin receptor / IRS activation / establishment of cell polarity / positive regulation of axon regeneration / positive regulation of cytokinesis / positive regulation of osteoblast proliferation / positive regulation of respiratory burst / amyloid-beta clearance / Respiratory syncytial virus (RSV) attachment and entry / regulation of embryonic development / positive regulation of receptor internalization / protein kinase activator activity / insulin receptor substrate binding / cellular response to angiotensin / response to vitamin E / G-protein alpha-subunit binding / epidermis development / positive regulation of glycogen biosynthetic process / phosphatidylinositol 3-kinase binding / Signal attenuation / SHC-related events triggered by IGF1R / transport across blood-brain barrier / negative regulation of MAPK cascade / peptidyl-tyrosine autophosphorylation / heart morphogenesis / estrous cycle / activation of protein kinase B activity / cellular response to transforming growth factor beta stimulus / dendrite membrane / Insulin receptor recycling / insulin-like growth factor receptor binding / T-tubule / phosphatidylinositol 3-kinase/protein kinase B signal transduction / neuron projection maintenance / cerebellum development / receptor-mediated endocytosis / axonogenesis / cellular response to dexamethasone stimulus / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of MAP kinase activity / insulin-like growth factor receptor signaling pathway / positive regulation of glycolytic process / hippocampus development / learning / positive regulation of D-glucose import / response to nicotine / positive regulation of smooth muscle cell proliferation / cellular response to estradiol stimulus / insulin receptor binding / cellular response to glucose stimulus / placental growth factor receptor activity / insulin receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / GPI-linked ephrin receptor activity / transmembrane-ephrin receptor activity Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.73 Å | |||||||||
![]() | Xu Y / Lawrence MC | |||||||||
Funding support | ![]()
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![]() | ![]() Title: How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor. Authors: Yibin Xu / Mai B Margetts / Hari Venugopal / John G Menting / Nicholas S Kirk / Tristan I Croll / Carlie Delaine / Briony E Forbes / Michael C Lawrence / ![]() ![]() Abstract: Monomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand ...Monomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand binding and signaling properties that differ from those of the homodimeric receptors. Here, we describe the cryoelectron microscopy structure of such a hybrid receptor in complex with insulin-like growth factor I (IGF-I). The structure (ca. 3.7 Å resolution) displays a single IGF-I ligand, bound in a similar fashion to that seen for IGFs in complex with IGF-1R. The IGF-I ligand engages the first leucine-rich-repeat domain and cysteine-rich region of the IGF-1R monomer (rather than those of the insulin receptor monomer), consistent with the determinants for IGF binding residing in the IGF-1R cysteine-rich region. The structure broadens our understanding of this receptor family and assists in delineating the key structural motifs involved in binding their respective ligands. | |||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 122.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.8 KB 13.8 KB | Display Display | ![]() |
Images | ![]() | 85.7 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 468.4 KB | Display | ![]() |
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Full document | ![]() | 467.9 KB | Display | |
Data in XML | ![]() | 6.9 KB | Display | |
Data in CIF | ![]() | 8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7s8vMC ![]() 7s0qC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Leg region of IGF1R/INSR | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : a complex of IGF-I with the ectodomain of a hybrid insulin recept...
Entire | Name: a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor |
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Components |
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-Supramolecule #1: a complex of IGF-I with the ectodomain of a hybrid insulin recept...
Supramolecule | Name: a complex of IGF-I with the ectodomain of a hybrid insulin receptor / type 1 insulin-like growth factor receptor type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 250 kDa/nm |
-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: 1 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 108.937242 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN ...String: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN NEYNYRCWTT NRCQKMCPST CGKRACTENN ECCHPECLGS CSAPDNDTAC VACRHYYYAG VCVPACPPNT YR FEGWRCV DRDFCANILS AESSDSEGFV IHDGECMQEC PSGFIRNGSQ SMYCIPCEGP CPKVCEEEKK TKTIDSVTSA QML QGCTIF KGNLLINIRR GNNIASELEN FMGLIEVVTG YVKIRHSHAL VSLSFLKNLR LILGEEQLEG NYSFYVLDNQ NLQQ LWDWD HRNLTIKAGK MYFAFNPKLC VSEIYRMEEV TGTKGRQSKG DINTRNNGER ASCESDVLHF TSTTTSKNRI IITWH RYRP PDYRDLISFT VYYKEAPFKN VTEYDGQDAC GSNSWNMVDV DLPPNKDVEP GILLHGLKPW TQYAVYVKAV TLTMVE NDH IRGAKSEILY IRTNASVPSI PLDVLSASNS SSQLIVKWNP PSLPNGNLSY YIVRWQRQPQ DGYLYRHNYC SKDKIPI RK YADGTIDIEE VTENPKTEVC GGEKGPCCAC PKTEAEKQAE KEEAEYRKVF ENFLHNSIFV PRPERKRRDV MQVANTTM S SRSRNTTAAD TYNITDPEEL ETEYPFFESR VDNKERTVIS NLRPFTLYRI DIHSCNHEAE KLGCSASNFV FARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN YTARIQATSL SGNGSWTDP VFFYVQAKTG YENFIHRMKQ LEDKVEELLS KNYHLENEVA RLKKLVGERS SSEQKLISEE DLN UniProtKB: Insulin-like growth factor 1 receptor |
-Macromolecule #2: Insulin receptor
Macromolecule | Name: Insulin receptor / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 109.809617 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNYIVLNK DDNEECGDIC P GTAKGKTN ...String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNYIVLNK DDNEECGDIC P GTAKGKTN CPATVINGQF VERCWTHSHC QKVCPTICKS HGCTAEGLCC HSECLGNCSQ PDDPTKCVAC RNFYLDGRCV ET CPPPYYH FQDWRCVNFS FCQDLHHKCK NSRRQGCHQY VIHNNKCIPE CPSGYTMNSS NLLCTPCLGP CPKVCHLLEG EKT IDSVTS AQELRGCTVI NGSLIINIRG GNNLAAELEA NLGLIEEISG YLKIRRSYAL VSLSFFRKLR LIRGETLEIG NYSF YALDN QNLRQLWDWS KHNLTITQGK LFFHYNPKLC LSEIHKMEEV SGTKGRQERN DIALKTNGDQ ASCENELLKF SYIRT SFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN VTEFDGQDAC GSNSWTVVDI DPPLRSNDPK SQNHPGWLMR GLKPWT QYA IFVKTLVTFS DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE RQAEDSE LF ELDYCLKGLK LPSRTWSPPF ESEDSQKHNQ SEYEDSAGEC CSCPKTDSQI LKELEESSFR KTFEDYLHNV VFVPRKTS S GTGAEDPRPS RKRRSLGDVG NVTVAVPTVA AFPNTSSTSV PTSPEEHRPF EKVVNKESLV ISGLRHFTGY RIELQACNQ DTPEERCSVA AYVSARTMPE AKADDIVGPV THEIFENNVV HLMWQEPKEP NGLIVLYEVS YRRYGDEELH LCVSRKHFAL ERGCRLRGL SPGNYSVRIR ATSLAGNGSW TEPTYFYVTD YLDVPSNIAR MKQLEDKVEE LLSKNYHLEN EVARLKKLVG E R UniProtKB: Insulin receptor |
-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: 5 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 1.44 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.73 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2.15.0) / Number images used: 151240 |
Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT / Overall B value: 45.7 |
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Output model | ![]() PDB-7s8v: |