+Open data
-Basic information
Entry | Database: PDB / ID: 7b1d | ||||||
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Title | Cryo-EM of Aedes Aegypti Toll5A | ||||||
Components | Toll-like receptor | ||||||
Keywords | IMMUNE SYSTEM / Mosquito vector biology / Toll receptor / LRR / Cystine knot domain | ||||||
Function / homology | Function and homology information toll-like receptor signaling pathway / transmembrane signaling receptor activity / innate immune response / membrane Similarity search - Function | ||||||
Biological species | Aedes aegypti (yellow fever mosquito) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å | ||||||
Authors | Gangloff, M. / Hardwick, S.W. / Chirgadze, D.Y. | ||||||
Funding support | United Kingdom, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7b1d.cif.gz | 261.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7b1d.ent.gz | 202.9 KB | Display | PDB format |
PDBx/mmJSON format | 7b1d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7b1d_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7b1d_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7b1d_validation.xml.gz | 57.1 KB | Display | |
Data in CIF | 7b1d_validation.cif.gz | 86 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b1/7b1d ftp://data.pdbj.org/pub/pdb/validation_reports/b1/7b1d | HTTPS FTP |
-Related structure data
Related structure data | 11984MC 7b1bC 7b1cC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 87675.773 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Aedes aegypti (yellow fever mosquito) / Gene: 5569408 / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: A0A6I8TEX2 #2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Toll5A-Spz1C complex / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 230 kDa/nm / Experimental value: YES | |||||||||||||||
Source (natural) | Organism: Aedes aegypti (yellow fever mosquito) | |||||||||||||||
Source (recombinant) | Organism: Drosophila melanogaster (fruit fly) | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK I / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K / Details: Blotting force 0 |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2700 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: ZEMLIN TABLEAU |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2 sec. / Electron dose: 51.1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 507268 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 85810 / Refinement type: OTHER / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 164.8 Å2 | ||||||||||||||||||||||||
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