+Open data
-Basic information
Entry | Database: PDB / ID: 7jgj | ||||||
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Title | IgA1 Protease in complex with neutralizing mAb | ||||||
Components |
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Keywords | IMMUNE SYSTEM / IgA1 / Protease / neutralization | ||||||
Function / homology | Function and homology information IgA-specific metalloendopeptidase / cell wall / metalloendopeptidase activity / membrane => GO:0016020 / proteolysis / zinc ion binding / extracellular region / membrane Similarity search - Function | ||||||
Biological species | Streptococcus pneumoniae (bacteria) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||
Authors | Eisenmesser, E.Z. / Zheng, H. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2020 Title: Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease. Authors: Zhiming Wang / Jeremy Rahkola / Jasmina S Redzic / Ying-Chih Chi / Norman Tran / Todd Holyoak / Hongjin Zheng / Edward Janoff / Elan Eisenmesser / Abstract: Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since ...Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since their discovery nearly 30 years ago despite the potential for developing vaccines that target these enzymes to block infection. Here we show through a series of cryo-electron microscopy single particle reconstructions how the Streptococcus pneumoniae IgA1 protease facilitates IgA1 substrate recognition and how this can be inhibited. Specifically, the Streptococcus pneumoniae IgA1 protease subscribes to an active-site-gated mechanism where a domain undergoes a 10.0 Å movement to facilitate cleavage. Monoclonal antibody binding inhibits this conformational change, providing a direct means to block infection at the host interface. These structural studies explain decades of biological and biochemical studies and provides a general strategy to block Streptococcus pneumoniae IgA1 protease activity to potentially prevent infection. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7jgj.cif.gz | 303.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jgj.ent.gz | 247.3 KB | Display | PDB format |
PDBx/mmJSON format | 7jgj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7jgj_validation.pdf.gz | 734.4 KB | Display | wwPDB validaton report |
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Full document | 7jgj_full_validation.pdf.gz | 765.4 KB | Display | |
Data in XML | 7jgj_validation.xml.gz | 50.6 KB | Display | |
Data in CIF | 7jgj_validation.cif.gz | 76.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jg/7jgj ftp://data.pdbj.org/pub/pdb/validation_reports/jg/7jgj | HTTPS FTP |
-Related structure data
Related structure data | 22328MC 6xjaC 6xjbC M: map data used to model this data 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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-Components
#1: Protein | Mass: 145095.812 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Streptococcus pneumoniae (bacteria) / Gene: iga, SPRM200_1016 / Production host: Escherichia coli (E. coli) / References: UniProt: A0A2U3RZX2, UniProt: Q59947*PLUS |
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#2: Antibody | Mass: 23270.615 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 23212.004 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 / Details: 20 mM HEPES, pH 7.4 150 mM NaCl | ||||||||||||||||||||||||
Buffer component | Conc.: 20 mM / Name: HEPES | ||||||||||||||||||||||||
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: OTHER |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 3 SIGMA CUT-OFF / Num. of particles: 64968 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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