+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11982 | |||||||||
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Title | Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C | |||||||||
Map data | EM map | |||||||||
Sample |
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Keywords | Mosquito vector biology / Toll receptor / LRR / Cystine knot domain / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information Toll binding / central nervous system formation / toll-like receptor signaling pathway / growth factor activity / transmembrane signaling receptor activity / inflammatory response / immune response / innate immune response / extracellular space / membrane Similarity search - Function | |||||||||
Biological species | Aedes aegypti (yellow fever mosquito) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.23 Å | |||||||||
Authors | Gangloff M / Hardwick SW / Chirgadze DY | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti. Authors: Yoann Saucereau / Thomas H Wilson / Matthew C K Tang / Martin C Moncrieffe / Steven W Hardwick / Dimitri Y Chirgadze / Sandro G Soares / Maria Jose Marcaida / Nicholas J Gay / Monique Gangloff / Abstract: Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone ...Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_11982.map.gz | 103.9 MB | EMDB map data format | |
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Header (meta data) | emd-11982-v30.xml emd-11982.xml | 21.3 KB 21.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11982_fsc.xml | 17.5 KB | Display | FSC data file |
Images | emd_11982.png | 117.3 KB | ||
Filedesc metadata | emd-11982.cif.gz | 6.8 KB | ||
Others | emd_11982_half_map_1.map.gz emd_11982_half_map_2.map.gz | 194.2 MB 194.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11982 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11982 | HTTPS FTP |
-Validation report
Summary document | emd_11982_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_11982_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_11982_validation.xml.gz | 21.1 KB | Display | |
Data in CIF | emd_11982_validation.cif.gz | 27.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11982 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11982 | HTTPS FTP |
-Related structure data
Related structure data | 7b1bMC 7b1cC 7b1dC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11982.map.gz / Format: CCP4 / Size: 209.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | EM map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map
File | emd_11982_half_map_1.map | ||||||||||||
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Annotation | Half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map
File | emd_11982_half_map_2.map | ||||||||||||
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Annotation | Half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C
Entire | Name: Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C |
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Components |
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-Supramolecule #1: Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C
Supramolecule | Name: Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Molecular weight | Theoretical: 230 KDa |
-Supramolecule #2: Toll-like receptor
Supramolecule | Name: Toll-like receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Aedes aegypti (yellow fever mosquito) |
-Supramolecule #3: AAEL013433-PA
Supramolecule | Name: AAEL013433-PA / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Aedes aegypti (yellow fever mosquito) |
-Macromolecule #1: Toll-like receptor
Macromolecule | Name: Toll-like receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Aedes aegypti (yellow fever mosquito) |
Molecular weight | Theoretical: 87.675773 KDa |
Recombinant expression | Organism: Drosophila melanocephala (fry) |
Sequence | String: TSTKRFTCPE ESEASNCSCE EFPSKTHFYC PDFNPTLYVD VEDRMRVDFK CYDEPHDFKS LPNLAIGSVK LLTVVDCVLD DDRPILESF KFLEVADVRS FVYNNHENGI RYNAKYFEGM EQLENLTLAR GVVSIDRDTF SGFLNLKRLT IEHNKLNLQP G TFEALSNL ...String: TSTKRFTCPE ESEASNCSCE EFPSKTHFYC PDFNPTLYVD VEDRMRVDFK CYDEPHDFKS LPNLAIGSVK LLTVVDCVLD DDRPILESF KFLEVADVRS FVYNNHENGI RYNAKYFEGM EQLENLTLAR GVVSIDRDTF SGFLNLKRLT IEHNKLNLQP G TFEALSNL TYLGLVYNGL NEIQPGLFDG LESLEALSLS YNDIKSLSAG SFNGLSSLRM LNLRVNKIES FDANTFASLK EL SRLEITL NPFVSLPRGL FSENKKLKTL ILTNNRKLVT LPEELLANLK ELTVVNLSHN GVGNLPESLL SGSSGIIELN LGY NRLNSL PEELLSDQPQ LQVLNLDHNQ LESIPDYFLE RNVELQTLYL SHNRLRSLSE KAFTKLKNLK ELHLENNQLQ TIPQ FLFSG TPKLEEIYMQ NNQLALHANS FINEELSIAD NDNTPFQVLQ KLRILHLRNN SISTIFQDWY INNLEMQSLD LSFNK LPGL SYTQLQFQSN ITLNLSNNEI SQVLLIDDLD LQPYQRINVD LNHNPLNCNC NALKFIQLIQ SKAEHGLQFN VDQLRC SEP PNLLDATMDQ LQTKDLLCDF ESADDCPKDC QCAMRLLDHT VIVNCSGRGL TEFPDLPIPS QLHEDFNALE VHVENNR LT KLPNLTKHNE ITQLYARNNS IQNLLPHNIP SKLRIIDLSQ NLLKMIDDST LAQINRSSHL ETIRLSQNQW LCDCPASS F LIFVQQNSRL ISDMSAIRCH PSGKSLDSIT VNELCFEDYT TENLYFQ UniProtKB: TIR domain-containing protein |
-Macromolecule #2: AAEL013433-PA
Macromolecule | Name: AAEL013433-PA / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Aedes aegypti (yellow fever mosquito) |
Molecular weight | Theoretical: 12.941044 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
Sequence | String: SDTANAPFLC ESEQLLIHPK EELSRNNSMV WIVNTKDYKQ GVRIEKCLKR QLGKPCNFCD ADTECKQLFH YRTLVAVDKV TKKPYKEQV LLPSCCKCAK ILSTGWSHPQ FEK UniProtKB: AAEL013433-PA |
-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: 3 / 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 | 5 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 12 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I / Details: Blotting force 0. |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 2.0 sec. / Average electron dose: 51.1 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.7 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: OTHER | ||||||||
Output model | PDB-7b1b: |