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Yorodumi- PDB-6rpt: Structure of tick complement inhibitor CirpT1 complexed with macr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6rpt | |||||||||
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Title | Structure of tick complement inhibitor CirpT1 complexed with macroglobubulin domain 4 of human complement C5 | |||||||||
Components |
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Keywords | IMMUNOSUPPRESSANT / complement / inhibitor / innate immunity / inflammation / C5 / terminal pathway inhibitor | |||||||||
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 / 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) Rhipicephalus pulchellus (arthropod) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | |||||||||
Authors | Reichhardt, M.P. / Lea, S.M. / Johnson, S. | |||||||||
Funding support | Finland, United Kingdom, 2items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6rpt.cif.gz | 254.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rpt.ent.gz | 196 KB | Display | PDB format |
PDBx/mmJSON format | 6rpt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6rpt_validation.pdf.gz | 478.1 KB | Display | wwPDB validaton report |
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Full document | 6rpt_full_validation.pdf.gz | 480.7 KB | Display | |
Data in XML | 6rpt_validation.xml.gz | 23.2 KB | Display | |
Data in CIF | 6rpt_validation.cif.gz | 31.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rp/6rpt ftp://data.pdbj.org/pub/pdb/validation_reports/rp/6rpt | HTTPS FTP |
-Related structure data
Related structure data | 4983C 6rqjC 5hccS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 14511.433 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: C5, CPAMD4 / Production host: Escherichia coli (E. coli) / References: UniProt: P01031 #2: Protein | Mass: 12284.823 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rhipicephalus pulchellus (arthropod) / Production host: Escherichia coli (E. coli) / References: UniProt: L7MB58 #3: Chemical | ChemComp-GOL / #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.55 Å3/Da / Density % sol: 51.76 % |
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Crystal grow | Temperature: 284.15 K / Method: vapor diffusion, sitting drop / Details: 0.02 M Na2PO4/K2PO4, 20 % w/v PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9762 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 8, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9762 Å / Relative weight: 1 |
Reflection | Resolution: 2.52→82.9 Å / Num. obs: 22552 / % possible obs: 99.8 % / Redundancy: 6.5 % / Rmerge(I) obs: 0.266 / Net I/σ(I): 3.8 |
Reflection shell | Resolution: 2.52→2.56 Å / Num. unique obs: 2243 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5HCC Resolution: 2.7→82.9 Å / Cross valid method: FREE R-VALUE
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Refinement step | Cycle: LAST / Resolution: 2.7→82.9 Å
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