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Yorodumi- EMDB-4983: Structure of human complement C5 complexed with tick inhibitors O... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4983 | |||||||||||||||
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Title | Structure of human complement C5 complexed with tick inhibitors OmCI, RaCI1 and CirpT1 | |||||||||||||||
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Sample |
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Function / homology | Function and homology information Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production / Peptide ligand-binding receptors ...Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / chemotaxis / toxin activity / G alpha (i) signalling events / killing of cells of another organism / cell surface receptor signaling pathway / inflammatory response / G protein-coupled receptor signaling pathway / signaling receptor binding / extracellular space / extracellular exosome / extracellular region Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Ornithodoros moubata (arthropod) / Rhipicephalus appendiculatus (arthropod) / Rhipicephalus pulchellus (arthropod) / Human (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||
Authors | Reichhardt MP / Johnson S / Lea SM | |||||||||||||||
Funding support | Finland, United Kingdom, 4 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2020 Title: An inhibitor of complement C5 provides structural insights into activation. Authors: Martin P Reichhardt / Steven Johnson / Terence Tang / Thomas Morgan / Nchimunya Tebeka / Niko Popitsch / Justin C Deme / Matthijs M Jore / Susan M Lea / Abstract: The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick lasts for days, and the tick must therefore rely on inhibitors to counter ...The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4983.map.gz | 70.9 MB | EMDB map data format | |
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Header (meta data) | emd-4983-v30.xml emd-4983.xml | 30.5 KB 30.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4983_fsc.xml | 10.3 KB | Display | FSC data file |
Images | emd_4983.png | 106.5 KB | ||
Masks | emd_4983_msk_1.map | 91.1 MB | Mask map | |
Others | emd_4983_additional_1.map.gz emd_4983_additional_2.map.gz emd_4983_half_map_1.map.gz emd_4983_half_map_2.map.gz | 58.2 MB 7.6 MB 71.2 MB 71.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4983 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4983 | HTTPS FTP |
-Validation report
Summary document | emd_4983_validation.pdf.gz | 444.2 KB | Display | EMDB validaton report |
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Full document | emd_4983_full_validation.pdf.gz | 443.3 KB | Display | |
Data in XML | emd_4983_validation.xml.gz | 16 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4983 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4983 | HTTPS FTP |
-Related structure data
Related structure data | 6rqjMC 6rptC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4983.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.822 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_4983_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #2
File | emd_4983_additional_1.map | ||||||||||||
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-Additional map: #1
File | emd_4983_additional_2.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_4983_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_4983_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
+Entire : Quaternary complex of human complement C5 with tick inhibitors Om...
+Supramolecule #1: Quaternary complex of human complement C5 with tick inhibitors Om...
+Supramolecule #2: Human Complement C5 (2)
+Supramolecule #3: Complement inhibitor
+Supramolecule #4: Rhipicephalus appendiculatus RaCI1
+Supramolecule #5: Putative 8.9 kDa family member
+Macromolecule #1: Complement C5
+Macromolecule #2: Complement inhibitor
+Macromolecule #3: Rhipicephalus appendiculatus RaCI1
+Macromolecule #4: Complement C5
+Macromolecule #5: Putative 8.9 kDa family member
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-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 / Number real images: 4440 / Average exposure time: 8.0 sec. / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |