[English] 日本語
Yorodumi
- EMDB-21415: Head region of the open conformation of the human type 1 insulin-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-21415
TitleHead 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.
Map dataFocused refinement
Sample
  • Complex: Head 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.
    • Complex: Insulin-like growth factor 1 receptor
      • Protein or peptide: Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain
    • Complex: Insulin-like growth factor IIInsulin-like growth factor 2
      • Protein or peptide: Insulin-like growth factor IIInsulin-like growth factor 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


spongiotrophoblast cell proliferation / cardiac atrium development / positive regulation of skeletal muscle tissue growth / negative regulation of cholangiocyte apoptotic process / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / regulation of muscle cell differentiation / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex ...spongiotrophoblast cell proliferation / cardiac atrium development / positive regulation of skeletal muscle tissue growth / negative regulation of cholangiocyte apoptotic process / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / regulation of muscle cell differentiation / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / protein transporter activity / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / insulin-like growth factor binding / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / genomic imprinting / positive regulation of DNA metabolic process / positive regulation of organ growth / protein localization to nuclear periphery / 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 / exocrine pancreas development / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / positive regulation of multicellular organism growth / insulin receptor activity / transcytosis / response to alkaloid / nitrogen catabolite activation of transcription from RNA polymerase II promoter / alphav-beta3 integrin-IGF-1-IGF1R complex / positive regulation of protein-containing complex disassembly / cellular response to angiotensin / cellular response to insulin-like growth factor stimulus / response to L-glutamate / positive regulation of vascular endothelial cell proliferation / dendritic spine maintenance / insulin binding / establishment of cell polarity / negative regulation of MAPK cascade / positive regulation of activated T cell proliferation / transmembrane receptor protein tyrosine kinase activator activity / positive regulation of axon regeneration / amyloid-beta clearance / positive regulation of cytokinesis / positive regulation of osteoblast proliferation / TFIID-class transcription factor complex binding / regulation of JNK cascade / positive regulation of cell division / estrous cycle / amino acid biosynthetic process / insulin receptor substrate binding / G-protein alpha-subunit binding / positive regulation of transcription initiation by RNA polymerase II / positive regulation of RNA polymerase II transcription preinitiation complex assembly / embryonic placenta development / response to vitamin E / positive regulation of glycogen biosynthetic process / SHC-related events triggered by IGF1R / phosphatidylinositol 3-kinase binding / positive regulation of insulin receptor signaling pathway / peptidyl-tyrosine autophosphorylation / cellular response to transforming growth factor beta stimulus / T-tubule / striated muscle cell differentiation / insulin-like growth factor receptor binding / cellular response to amino acid starvation / protein serine/threonine kinase activator activity / cerebellum development / cellular response to dexamethasone stimulus / axonogenesis / insulin-like growth factor receptor signaling pathway / positive regulation of mitotic nuclear division / platelet alpha granule lumen / response to nicotine / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to estradiol stimulus / caveola / cellular response to glucose stimulus / hippocampus development / animal organ morphogenesis / positive regulation of smooth muscle cell proliferation / growth factor activity / insulin receptor binding / hormone activity / receptor protein-tyrosine kinase / osteoblast differentiation / cellular response to mechanical stimulus / RNA polymerase II transcription regulator complex / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / glucose metabolic process / :
Similarity search - Function
Insulin-like growth factor II E-peptide, C-terminal / Insulin-like growth factor II / Insulin-like growth factor II E-peptide / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain superfamily ...Insulin-like growth factor II E-peptide, C-terminal / Insulin-like growth factor II / Insulin-like growth factor II E-peptide / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain superfamily / Basic-leucine zipper domain / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / 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 III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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
Similarity search - Domain/homology
Insulin-like growth factor II / General control transcription factor GCN4 / Insulin-like growth factor 1 receptor
Similarity search - Component
Biological speciesHomo sapiens (human) / Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (yeast)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.21 Å
AuthorsXu Y / Kirk NS / Lawrence MC / Croll TI
Funding support Australia, United Kingdom, 2 items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)APP1128553 Australia
Wellcome Trust209407/Z/17/ United Kingdom
CitationJournal: Structure / Year: 2020
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.
History
DepositionFeb 19, 2020-
Header (metadata) releaseMay 13, 2020-
Map releaseMay 13, 2020-
UpdateJul 29, 2020-
Current statusJul 29, 2020Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.5
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.5
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6vwg
  • Surface level: 0.5
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6vwg
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_21415.png

Downloads & links

-
Map

FileDownload / File: emd_21415.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationFocused refinement
Voxel sizeX=Y=Z: 1.06 Å
Density
Contour LevelBy AUTHOR: 0.5 / Movie #1: 0.5
Minimum - Maximum-1.628183 - 4.5414824
Average (Standard dev.)0.0012422632 (±0.039938852)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 423.99997 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.061.061.06
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z424.000424.000424.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-1.6284.5410.001

-
Supplemental data

-
Sample components

-
Entire : Head region of the open-leg conformation of the human type 1 insu...

EntireName: Head 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.
Components
  • Complex: Head 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.
    • Complex: Insulin-like growth factor 1 receptor
      • Protein or peptide: Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain
    • Complex: Insulin-like growth factor IIInsulin-like growth factor 2
      • Protein or peptide: Insulin-like growth factor IIInsulin-like growth factor 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: Head region of the open-leg conformation of the human type 1 insu...

SupramoleculeName: Head 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 / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 250 KDa

-
Supramolecule #2: Insulin-like growth factor 1 receptor

SupramoleculeName: Insulin-like growth factor 1 receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Escherichia coli (E. coli)

-
Supramolecule #3: Insulin-like growth factor II

SupramoleculeName: Insulin-like growth factor II / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2

-
Macromolecule #1: Leucine-zippered human type 1 insulin-like growth factor receptor...

MacromoleculeName: Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain
type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase
Source (natural)Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (yeast)
Strain: ATCC 204508 / S288c
Molecular weightTheoretical: 108.937242 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: 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

-
Macromolecule #2: Insulin-like growth factor II

MacromoleculeName: Insulin-like growth factor II / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.484472 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
AYRPSETLCG GELVDTLQFV CGDRGFYFSR PASRVSRRSR GIVEECCFRS CDLALLETYC ATPAKSE

-
Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.1 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormula
24.8 mMTris-HClTris
137.0 mMNaClSodium chloride
2.7 mMKCl
0.02 %NaN3
GridModel: Quantifoil, UltrAuFoil, R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Details: 15mA current
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
DetailsIGFII:IGF-1R molar ratio 1.5:1

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm
Specialist opticsEnergy filter - Name: GIF Quantum LS
Sample stageCooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 4585 / Average exposure time: 10.0 sec. / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Particle selectionNumber selected: 2057701
CTF correctionSoftware - Name: CTFFIND (ver. 4.1.13)
Startup modelType of model: OTHER
Details: Initial model was of the same ectodomain construct in complex with IGF-I (unpublished data).
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.11)
Final 3D classificationNumber classes: 7 / Software - Name: cryoSPARC (ver. 2.11)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.11)
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2.11) / Number images used: 205471

-
Atomic model buiding 1

Initial modelPDB ID:

5u8r

DetailsUCSF Chimera was used for the initial fitting and ISOLDE v 1.03b was using for flexible fitting.
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-6vwg:
Head 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.

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more