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- EMDB-12761: Anthrax toxin prepore in complex with the neutralizing Fab cAb29 -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12761 | |||||||||
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Title | Anthrax toxin prepore in complex with the neutralizing Fab cAb29 | |||||||||
![]() | Anthrax toxin prepore in complex with the neutralizing Fab cAb29 | |||||||||
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Function / homology | ![]() positive regulation of apoptotic process in another organism / host cell cytosol / negative regulation of MAPK cascade / Uptake and function of anthrax toxins / host cell endosome membrane / protein homooligomerization / toxin activity / host cell plasma membrane / extracellular region / identical protein binding ...positive regulation of apoptotic process in another organism / host cell cytosol / negative regulation of MAPK cascade / Uptake and function of anthrax toxins / host cell endosome membrane / protein homooligomerization / toxin activity / host cell plasma membrane / extracellular region / identical protein binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Hoelzgen F / Zalk R / Alcalay R / Cohen-Schwartz S / Garau G / Shahar A / Mazor O / Frank GA | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane-penetrating loop. Authors: F Hoelzgen / R Zalk / R Alcalay / S Cohen-Schwartz / G Garau / A Shahar / O Mazor / G A Frank / ![]() ![]() Abstract: Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus ...Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is one of two major virulence factors of Bacillus anthracis, the causative agent of anthrax disease. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the cytotoxic enzymes of the toxin are extruded. The PA pore is formed by a cooperative conformational change in which the membrane-penetrating loops of PA associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target for monoclonal antibody-based therapy. cAb29 is a highly effective neutralizing antibody against PA. Here, the cryo-EM structure of PA in complex with the Fab portion of cAb29 was determined. It was found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to the static surface-exposed loop of the D3 domain of the same subunit, thereby preventing pore formation. These results provide the structural basis for the antibody-based neutralization of PA and bring into focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines. #1: ![]() Title: Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane penetrating loop Authors: Hoelzgen F / Zalk R / Alcalay R / Garau G / Shahar A / Mazor O / Frank GA | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 13.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.3 KB 14.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.1 KB | Display | ![]() |
Images | ![]() | 121.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 244 KB | Display | ![]() |
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Full document | ![]() | 243.2 KB | Display | |
Data in XML | ![]() | 13.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7o85MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Anthrax toxin prepore in complex with the neutralizing Fab cAb29 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Fab bound to anthrax protective antigen
Entire | Name: Fab bound to anthrax protective antigen |
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Components |
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-Supramolecule #1: Fab bound to anthrax protective antigen
Supramolecule | Name: Fab bound to anthrax protective antigen / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 791 KDa |
-Supramolecule #2: anthrax protective antigen
Supramolecule | Name: anthrax protective antigen / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Supramolecule #3: Fab
Supramolecule | Name: Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Protective antigen PA-63
Macromolecule | Name: Protective antigen PA-63 / type: protein_or_peptide / ID: 1 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 49.244438 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: TVPDRDNDGI PDSLEVEGYT VDVKNKRTFL SPWISNIHEK KGLTKYKSSP EKWSTASDPY SDFEKVTGRI DKNVSPEARH PLVAAYPIV HVDMENIILS KNEDQSTQNT DSQTRTISKN TSTSRTHTSE VHGNAEVHAS FFDIGGSVSA GFSNSNSSTV A IDHSLSLA ...String: TVPDRDNDGI PDSLEVEGYT VDVKNKRTFL SPWISNIHEK KGLTKYKSSP EKWSTASDPY SDFEKVTGRI DKNVSPEARH PLVAAYPIV HVDMENIILS KNEDQSTQNT DSQTRTISKN TSTSRTHTSE VHGNAEVHAS FFDIGGSVSA GFSNSNSSTV A IDHSLSLA GERTWAETMG LNTADTARLN ANIRYVNTGT APIYNVLPTT SLVLGKNQTL ATIKAKENQL SQILAPNNYY PS KNLAPIA LNAQDDFSST PITMNYNQFL ELEKTKQLRL DTDQVYGNIA TYNFENGRVR VDTGSNWSEV LPQIQETTAR IIF NGKDLN LVERRIAAVN PSDPLETTKP DMTLKEALKI AFGFNEPNGN LQYQGKDITE FDFNFDQQTS QNIKNQLAEL NATN IYTVL DKIKLNAKMN ILIRDKRFHY DRNNIAVGAD ESVVKE |
-Macromolecule #2: Fab
Macromolecule | Name: Fab / type: protein_or_peptide / ID: 2 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 10.023125 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: AAAAAAAAAA AAAAAAAAAA ISCRASQDIS NYLNWYAAAA AAAAALLIYY TSRLHSEVPS RFSGSGSGTD YSLTIAAAAA AAAAAAFCQ QGKTLPWTFG GGTKL |
-Macromolecule #3: Fab
Macromolecule | Name: Fab / type: protein_or_peptide / ID: 3 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 10.58668 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: AAAAAAAAAA AAAAAAAAAA AAKASGYIFT NYNMHWVAAA AAAAAEWIGA IYPRTGDTSY NQKFKGKATL TADKSSSTAY AAAAAAAAA AAAAAACARD GFAYWAAAAA AAAA |
-Macromolecule #4: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 4 / Number of copies: 14 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |