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- EMDB-16718: Drosophila melanogaster insulin receptor ectodomain in complex wi... -

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Basic information

Entry
Database: EMDB / ID: EMD-16718
TitleDrosophila melanogaster insulin receptor ectodomain in complex with DILP5
Map dataPrimary Map masked
Sample
  • Complex: Drosophila insulin receptor ectodomain with DILP-5
    • Complex: Drosophila insulin-like peptide 5
      • Protein or peptide: Probable insulin-like peptide 5 A chain
      • Protein or peptide: Probable insulin-like peptide 5
    • Protein or peptide: Insulin-like receptor
KeywordsDILP5 hormone / Drosophila insulin-like signalling receptor / disulfide linked ectodomain / SIGNALING PROTEIN
Function / homology
Function and homology information


primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / germ-line stem-cell niche homeostasis / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / male germ-line stem cell asymmetric division ...primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / germ-line stem-cell niche homeostasis / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / male germ-line stem cell asymmetric division / embryonic development via the syncytial blastoderm / female germ-line stem cell population maintenance / germ-band shortening / negative regulation of circadian sleep/wake cycle, sleep / carbohydrate homeostasis / imaginal disc growth / open tracheal system development / germ-line stem cell division / positive regulation of neuron remodeling / follicle cell of egg chamber development / lymph gland development / intestinal stem cell homeostasis / female germ-line stem cell asymmetric division / positive regulation of border follicle cell migration / positive regulation of fat cell proliferation / positive regulation of organ growth / positive regulation of lipid storage / insulin receptor complex / positive regulation of multicellular organism growth / regulation of organ growth / insulin receptor activity / sleep / triglyceride homeostasis / embryo development ending in birth or egg hatching / insulin binding / positive regulation of wound healing / positive regulation of neuroblast proliferation / negative regulation of feeding behavior / female gonad development / lipid homeostasis / positive regulation of cell size / regulation of multicellular organism growth / insulin receptor substrate binding / developmental growth / phosphatidylinositol 3-kinase binding / cellular response to starvation / negative regulation of autophagy / locomotory behavior / response to cocaine / cholesterol homeostasis / determination of adult lifespan / cell surface receptor protein tyrosine kinase signaling pathway / axon guidance / insulin receptor binding / multicellular organism growth / hormone activity / receptor protein-tyrosine kinase / SH3 domain binding / circadian rhythm / insulin receptor signaling pathway / glucose homeostasis / nervous system development / regulation of cell population proliferation / positive regulation of cell growth / protein tyrosine kinase activity / response to oxidative stress / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor ligand activity / axon / protein phosphorylation / positive regulation of cell population proliferation / extracellular space / extracellular region / ATP binding / identical protein binding / metal ion binding / plasma membrane
Similarity search - Function
Insulin-related peptide, invertebrates / Long hematopoietin receptor, single chain family signature. / 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-related peptide, invertebrates / Long hematopoietin receptor, single chain family signature. / 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 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 receptor / Probable insulin-like peptide 5
Similarity search - Component
Biological speciesDrosophila melanogaster (fruit fly)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsViola CM / Brzozowski AM / Shafi T
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MR/R009066/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/W003783/1 United Kingdom
CitationJournal: Nat Commun / Year: 2023
Title: Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.
Authors: Cristina M Viola / Orsolya Frittmann / Huw T Jenkins / Talha Shafi / Pierre De Meyts / Andrzej M Brzozowski /
Abstract: The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the ...The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric 'T' conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism.
History
DepositionFeb 17, 2023-
Header (metadata) releaseDec 20, 2023-
Map releaseDec 20, 2023-
UpdateDec 20, 2023-
Current statusDec 20, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_16718.png

Downloads & links

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Map

FileDownload / File: emd_16718.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPrimary Map masked
Voxel sizeX=Y=Z: 1.01322 Å
Density
Contour LevelBy AUTHOR: 0.018
Minimum - Maximum-0.04995313 - 0.106235065
Average (Standard dev.)0.00015611654 (±0.0019096341)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 364.7592 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_16718_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: First unfiltered half map unmasked from Relion Refine3D

Fileemd_16718_half_map_1.map
AnnotationFirst unfiltered half map unmasked from Relion Refine3D
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Second unfiltered half map unmasked from Relion Refine3D

Fileemd_16718_half_map_2.map
AnnotationSecond unfiltered half map unmasked from Relion Refine3D
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : Drosophila insulin receptor ectodomain with DILP-5

EntireName: Drosophila insulin receptor ectodomain with DILP-5
Components
  • Complex: Drosophila insulin receptor ectodomain with DILP-5
    • Complex: Drosophila insulin-like peptide 5
      • Protein or peptide: Probable insulin-like peptide 5 A chain
      • Protein or peptide: Probable insulin-like peptide 5
    • Protein or peptide: Insulin-like receptor

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Supramolecule #1: Drosophila insulin receptor ectodomain with DILP-5

SupramoleculeName: Drosophila insulin receptor ectodomain with DILP-5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Drosophila melanogaster (fruit fly)
Molecular weightTheoretical: 5.8 KDa

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Supramolecule #2: Drosophila insulin-like peptide 5

SupramoleculeName: Drosophila insulin-like peptide 5 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Drosophila melanogaster (fruit fly)

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Macromolecule #1: Insulin-like receptor

MacromoleculeName: Insulin-like receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase
Source (natural)Organism: Drosophila melanogaster (fruit fly)
Molecular weightTheoretical: 120.074641 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MHNYSYSPGI SLLLFILLAN TLAIQAVVLP AHQQHLLHND IADGLDKTAL SVSGTQSRWT RSESNPTMRL SQNVKPCKSM DIRNMVSHF NQLENCTVIE GFLLIDLIND ASPLNRSFPK LTEVTDYIII YRVTGLHSLS KIFPNLSVIR GNKLFDGYAL V VYSNFDLM ...String:
MHNYSYSPGI SLLLFILLAN TLAIQAVVLP AHQQHLLHND IADGLDKTAL SVSGTQSRWT RSESNPTMRL SQNVKPCKSM DIRNMVSHF NQLENCTVIE GFLLIDLIND ASPLNRSFPK LTEVTDYIII YRVTGLHSLS KIFPNLSVIR GNKLFDGYAL V VYSNFDLM DLGLHKLRSI TRGGVRIEKN HKLCYDRTID WLEILAENET QLVVLTENGK EKECRLSKCP GEIRIEEGHD TT AIEGELN ASCQLHNNRR LCWNSKLCQT KCPEKCRNNC IDEHTCCSQD CLGGCVIDKN GNESCISCRN VSFNNICMDS CPK GYYQFD SRCVTANECI TLTKFETNSV YSGIPYNGQC ITHCPTGYQK SENKRMCEPC PGGKCDKECS SGLIDSLERA REFH GCTII TGTEPLTISI KRESGAHVMD ELKYGLAAVH KIQSSLMVHL TYGLKSLKFF QSLTEISGDP PMDADKYALY VLDNR DLDE LWGPNQTVFI RKGGVFFHFN PKLCVSTINQ LLPMLASKPK FFEKSDVGAD SNGNRGSCGT AVLNVTLQSV GANSAM LNV TTKVEIGEPQ KPSNATIVFK DPRAFIGFVF YHMIDPYGNS TKSSDDPCDD RWKVSSPEKS GVMVLSNLIP YTNYSYY VR TMAISSELTN AESDVKNFRT NPGRPSKVTE VVATAISDSK INVTWSYLDK PYGVLTRYFI KAKLINRPTR NNNRDYCT E PLVKAMENDL PATTPTKKIS DPLAGDCKCV EGSKKTSSQE YDDRKVQAGM EFENALQNFI FVPNIRKSKN GSSDKSDGA EGAALDSNAI PNGGATNPSR RRRDVALEPE LDDVEGSVLL RHVRSITDDT DAFFEKDDEN TYKDEEDLSS NKQFYEVFAK ELPPNQTHF VFEKLRHFTR YAIFVVACRE EIPSEKLRDT SFKKSLCSDY DTVFQTTKRK KFADIVMDLK VDLEHANNTE S PVRVRWTP PVDPNGEIVT YEVAYKLQKP DQVEEKKCIP AADFNQTAGY LIKLNEGLYS FRVRANSIAG YGDFTEVEHI KV EPPPSYA KDEVLFQGPS RSAWSHPQFE K

UniProtKB: Insulin-like receptor

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Macromolecule #2: Probable insulin-like peptide 5 A chain

MacromoleculeName: Probable insulin-like peptide 5 A chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Drosophila melanogaster (fruit fly)
Molecular weightTheoretical: 2.795097 KDa
SequenceString:
DFRGVVDSCC RNSCSFSTLR AYCDS

UniProtKB: Probable insulin-like peptide 5

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Macromolecule #3: Probable insulin-like peptide 5

MacromoleculeName: Probable insulin-like peptide 5 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Drosophila melanogaster (fruit fly)
Molecular weightTheoretical: 3.018603 KDa
SequenceString:
NSLRACGPAL MDMLRVACPN GFNSMFAK

UniProtKB: Probable insulin-like peptide 5

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 4.0 µm / Nominal defocus min: 0.5 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Average electron dose: 0.829 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 129444
FSC plot (resolution estimation)

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Atomic model buiding 1

DetailsLocal fitting of Alphafold predicted domains was done using ChimeraX
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-8cls:
Drosophila melanogaster insulin receptor ectodomain in complex with DILP5

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