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Open data
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Basic information
Entry | Database: PDB / ID: 6xja | ||||||
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Title | Streptococcus Pneumoniae IgA1 Protease with IgA1 substrate | ||||||
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![]() | IMMUNE SYSTEM / IgA1 / Complex / Protease / metalloprotease | ||||||
Function / homology | ![]() IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / transcription factor TFIIIB complex / RNA polymerase III preinitiation complex assembly / glomerular filtration / TFIIIC-class transcription factor complex binding / IgA immunoglobulin complex / IgG immunoglobulin complex ...IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / transcription factor TFIIIB complex / RNA polymerase III preinitiation complex assembly / glomerular filtration / TFIIIC-class transcription factor complex binding / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / complement activation, classical pathway / Cell surface interactions at the vascular wall / antigen binding / 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 | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
![]() | Eisenmesser, E.Z. / Zheng, H. | ||||||
Funding support | ![]()
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![]() | ![]() 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. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 374.8 KB | Display | ![]() |
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PDB format | ![]() | 304.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 848 KB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 92.4 KB | Display | |
Data in CIF | ![]() | 129 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22204MC ![]() 6xjbC ![]() 7jgjC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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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.) ![]() Strain: ATCC BAA-255 / R6 / Gene: iga, spr1042 / Production host: ![]() ![]() 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) ![]() #3: Antibody | | Mass: 21947.256 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #4: Protein | | Mass: 21930.480 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Value: 0.3 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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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 | ||||||||||||||||||||||||
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