+Open data
-Basic information
Entry | Database: PDB / ID: 6xja | ||||||
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Title | Streptococcus Pneumoniae IgA1 Protease with IgA1 substrate | ||||||
Components |
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Keywords | IMMUNE SYSTEM / IgA1 / Complex / Protease / metalloprotease | ||||||
Function / homology | Function and homology information IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating ...IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating / complement activation, classical pathway / antigen binding / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / metalloendopeptidase activity / antibacterial humoral response / adaptive immune response / blood microparticle / immune response / proteolysis / extracellular space / zinc ion binding / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Streptococcus pneumoniae (bacteria) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 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 | 6xja.cif.gz | 374.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xja.ent.gz | 304.1 KB | Display | PDB format |
PDBx/mmJSON format | 6xja.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6xja_validation.pdf.gz | 848 KB | Display | wwPDB validaton report |
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Full document | 6xja_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 6xja_validation.xml.gz | 92.4 KB | Display | |
Data in CIF | 6xja_validation.cif.gz | 129 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xj/6xja ftp://data.pdbj.org/pub/pdb/validation_reports/xj/6xja | HTTPS FTP |
-Related structure data
Related structure data | 22204MC 6xjbC 7jgjC 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: 145926.625 Da / Num. of mol.: 1 / Mutation: E1605A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Streptococcus pneumoniae (strain ATCC BAA-255 / R6) (bacteria) Strain: ATCC BAA-255 / R6 / Gene: iga, spr1042 / Production host: Escherichia coli (E. coli) References: UniProt: Q59947, IgA-specific metalloendopeptidase | ||||
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#2: Protein | Mass: 22887.988 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01876 #3: Antibody | | Mass: 21947.256 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) #4: Protein | | Mass: 21930.480 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) 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
Component |
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Molecular weight | Value: 0.3 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Escherichia coli (E. coli) | ||||||||||||||||||||||||
Buffer solution | pH: 7 / Details: 20 mM Hepes, pH 7 150 mM NaCl | ||||||||||||||||||||||||
Specimen | 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_3758: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 3 SIGMA CUT-OFF / Num. of particles: 100000 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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