+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11814 | |||||||||||||||
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Title | The cryo-EM structure of the Vag8-C1 inhibitor complex | |||||||||||||||
Map data | post-processed final volume | |||||||||||||||
Sample |
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Function / homology | Function and homology information negative regulation of complement activation, lectin pathway / Defective SERPING1 causes hereditary angioedema / outer membrane / blood circulation / complement activation, classical pathway / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / platelet alpha granule lumen / Regulation of Complement cascade / serine-type endopeptidase inhibitor activity ...negative regulation of complement activation, lectin pathway / Defective SERPING1 causes hereditary angioedema / outer membrane / blood circulation / complement activation, classical pathway / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / platelet alpha granule lumen / Regulation of Complement cascade / serine-type endopeptidase inhibitor activity / blood coagulation / Platelet degranulation / collagen-containing extracellular matrix / blood microparticle / endoplasmic reticulum lumen / innate immune response / extracellular space / extracellular exosome / extracellular region Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Bordetella pertussis (bacteria) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||||||||
Authors | Johnson S / Lea SM / Deme JC / Furlong E / Dhillon A | |||||||||||||||
Funding support | United Kingdom, 4 items
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Citation | Journal: mBio / Year: 2021 Title: Molecular Basis for Bordetella pertussis Interference with Complement, Coagulation, Fibrinolytic, and Contact Activation Systems: the Cryo-EM Structure of the Vag8-C1 Inhibitor Complex. Authors: Arun Dhillon / Justin C Deme / Emily Furlong / Dorina Roem / Ilse Jongerius / Steven Johnson / Susan M Lea / Abstract: Complement, contact activation, coagulation, and fibrinolysis are serum protein cascades that need strict regulation to maintain human health. Serum glycoprotein, a C1 inhibitor (C1-INH), is a key ...Complement, contact activation, coagulation, and fibrinolysis are serum protein cascades that need strict regulation to maintain human health. Serum glycoprotein, a C1 inhibitor (C1-INH), is a key regulator (inhibitor) of serine proteases of all the above-mentioned pathways. Recently, an autotransporter protein, virulence-associated gene 8 (Vag8), produced by the whooping cough pathogen, , was shown to bind to C1-INH and interfere with its function. Here, we present the structure of the Vag8-C1-INH complex determined using cryo-electron microscopy at a 3.6-Å resolution. The structure shows a unique mechanism of C1-INH inhibition not employed by other pathogens, where Vag8 sequesters the reactive center loop of C1-INH, preventing its interaction with the target proteases. The structure of a 10-kDa protein complex is one of the smallest to be determined using cryo-electron microscopy at high resolution. The structure reveals that C1-INH is sequestered in an inactivated state by burial of the reactive center loop in Vag8. By so doing, the bacterium is able to simultaneously perturb the many pathways regulated by C1-INH. Virulence mechanisms such as the one described here assume more importance given the emerging evidence about dysregulation of contact activation, coagulation, and fibrinolysis leading to COVID-19 pneumonia. | |||||||||||||||
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_11814.map.gz | 8.9 MB | EMDB map data format | |
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Header (meta data) | emd-11814-v30.xml emd-11814.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11814_fsc.xml | 11.7 KB | Display | FSC data file |
Images | emd_11814.png | 148.2 KB | ||
Masks | emd_11814_msk_1.map | 134.6 MB | Mask map | |
Others | emd_11814_additional_1.map.gz emd_11814_additional_2.map.gz emd_11814_half_map_1.map.gz emd_11814_half_map_2.map.gz | 105.9 MB 83 MB 106.1 MB 106.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11814 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11814 | HTTPS FTP |
-Validation report
Summary document | emd_11814_validation.pdf.gz | 354.7 KB | Display | EMDB validaton report |
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Full document | emd_11814_full_validation.pdf.gz | 353.8 KB | Display | |
Data in XML | emd_11814_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | emd_11814_validation.cif.gz | 24.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11814 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11814 | HTTPS FTP |
-Related structure data
Related structure data | 7akvMC 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_11814.map.gz / Format: CCP4 / Size: 134.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | post-processed final volume | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.828 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_11814_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: refinement volume
File | emd_11814_additional_1.map | ||||||||||||
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Annotation | refinement volume | ||||||||||||
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Density Histograms |
-Additional map: relion local resolution filtered volume
File | emd_11814_additional_2.map | ||||||||||||
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Annotation | relion local resolution filtered volume | ||||||||||||
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Density Histograms |
-Half map: second half map
File | emd_11814_half_map_1.map | ||||||||||||
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Annotation | second half map | ||||||||||||
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Density Histograms |
-Half map: first half map
File | emd_11814_half_map_2.map | ||||||||||||
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Annotation | first half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Vag8:C1 inhibitor complex
Entire | Name: Vag8:C1 inhibitor complex |
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Components |
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-Supramolecule #1: Vag8:C1 inhibitor complex
Supramolecule | Name: Vag8:C1 inhibitor complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 100 KDa |
-Macromolecule #1: Plasma protease C1 inhibitor
Macromolecule | Name: Plasma protease C1 inhibitor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.011637 KDa |
Recombinant expression | Organism: Drosophila albipalpis (fry) |
Sequence | String: PTIQPTQPTT QLPTDSPTQP TTGSFCPGPV TLCSDLESHS TEAVLGDALV DFSLKLYHAF SAMKKVETNM AFSPFSIASL LTQVLLGAG ENTKTNLESI LSYPKDFTCV HQALKGFTTK GVTSVSQIFH SPDLAIRDTF VNASRTLYSS SPRVLSNNSD A NLELINTW ...String: PTIQPTQPTT QLPTDSPTQP TTGSFCPGPV TLCSDLESHS TEAVLGDALV DFSLKLYHAF SAMKKVETNM AFSPFSIASL LTQVLLGAG ENTKTNLESI LSYPKDFTCV HQALKGFTTK GVTSVSQIFH SPDLAIRDTF VNASRTLYSS SPRVLSNNSD A NLELINTW VAKNTNNKIS RLLDSLPSDT RLVLLNAIYL SAKWKTTFDP KKTRMEPFHF KNSVIKVPMM NSKKYPVAHF ID QTLKAKV GQLQLSHNLS LVILVPQNLK HRLEDMEQAL SPSVFKAIME KLEMSKFQPT LLTLPRIKVT TSQDMLSIME KLE FFDFSY DLNLCGLTED PDLQVSAMQH QTVLELTETG VEAAAASAIS VARTLLVFEV QQPFLFVLWD QQHKFPVFMG RVYD PRA |
-Macromolecule #2: Vag8
Macromolecule | Name: Vag8 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bordetella pertussis (bacteria) |
Molecular weight | Theoretical: 91.262172 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: AVTAAQRIDG GAAFLGDVAI ATTKASEHGI NVTGRTAEVR VTGGTIRTSG NQAQGLRVGT ENAPDNTAVV ASVFLQNLII ETSGTGALG VSVHEPQGGG GTRLSMSGTT VRTRGDDSFA LQLSGPASAT LNDVALETAG QQAPAVVLWQ GAQLNAQGLV V QVNGAGVS ...String: AVTAAQRIDG GAAFLGDVAI ATTKASEHGI NVTGRTAEVR VTGGTIRTSG NQAQGLRVGT ENAPDNTAVV ASVFLQNLII ETSGTGALG VSVHEPQGGG GTRLSMSGTT VRTRGDDSFA LQLSGPASAT LNDVALETAG QQAPAVVLWQ GAQLNAQGLV V QVNGAGVS AIHAQDAGSF TLSGSDITAR GLEVVGIYVQ EGMQGTLTGT RVTTQGDTAP ALQVEDAGTH VSMNGGALST SG ANSPAAW LLAGGSAQFR DTVLRTVGEA SHGVDVAAHS EVELAHAQVR ADGQGAHGLV VTRSSAMVRA GSLVESTGDG AAA LLESGH LTVDGSVVHG HGAAGLEVDG ESNVSLLNGA RLSSDQPTAI RLIDPRSVLN LDIKDRAQLL GDIAPEAQQP DGSP EQARV RVALADGGTW AGRTDGAVHT VRLLDRGVWT VTGDSRVAEV KLEGGTLAFA PPAQPKGAFK TLVATQGISG TGTIV MNAH LPSGTADVLV APQGFGDRQV LVVNNTDDGT ESGATKVPLI EDEQGHTAFT LGNMGGRVDA GARQYELTAS EAQADK ART WQLTPTNELS TTATAAVNAM AIAASQRIWQ AEMDVLLRHM SGLHSIGSPG GFWARGLSQR QRLDTGYGPW QKQTVSG IE LGLDRRVAGG ATTAWSVGML AGYSETRRDG GAYRAGHVHS AHVGAYVSYL NDSGSYVDGV VKYNRFRHGF DIRTTDLK R VDAKHRSHGL GALLRGGRRI DIDGGWYVEP QASVAWFHAG GSRYEASNGL RVRADGAHSW VLRAGAEAGR QMRLANGNI VEPYARLGWA QELGADNAVY TNGIRHVTRS RGGFAEARVG VGALLGKRHA LYADYEYAKG ARFEAPWTLQ LGYRYSW |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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Output model | PDB-7akv: |