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Open data
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Basic information
Entry | Database: PDB / ID: 8yl5 | ||||||
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Title | The DSR2-DSAD1 complex with DSAD1 on the same sides | ||||||
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![]() | IMMUNE SYSTEM / complex | ||||||
Function / homology | : / Uncharacterized protein![]() | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.45 Å | ||||||
![]() | Yang, X. / Zheng, J. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into autoinhibition and activation of defense-associated sirtuin protein. Authors: Xu Yang / Yiqun Wang / Jianting Zheng / ![]() Abstract: Bacterial defense-associated sirtuin 2 (DSR2) proteins harbor an N-terminal sirtuin (SIR2) domain degrading NAD. DSR2 from Bacillus subtilis 29R is autoinhibited and unable to hydrolyze NAD in the ...Bacterial defense-associated sirtuin 2 (DSR2) proteins harbor an N-terminal sirtuin (SIR2) domain degrading NAD. DSR2 from Bacillus subtilis 29R is autoinhibited and unable to hydrolyze NAD in the absence of phage infection. A tail tube protein (TTP) of phage SPR activates the DSR2 while a DSR2-inhibiting protein of phage SPbeta, known as DSAD1 (DSR anti-defense 1), inactivates the DSR2. Although DSR2 structures in complexed with TTP and DSAD1, respectively, have been reported recently, the autoinhibition and activation mechanisms remain incompletely understood. Here, we present cryo-electron microscopy structures of the DSR2-NAD complex in autoinhibited state and the in vitro assembled DSR2-TFD (TTP tube-forming domain) complex in activated state. The DSR2-NAD complex reveals that the autoinhibited DSR2 assembles into an inactive tetramer, binding NAD through a distinct pocket situated outside active site. Binding of TFD into cavities within the sensor domains of DSR2 triggers a conformational change in SIR2 regions, activating its NADase activity, whereas the TTP β-sandwich domain (BSD) is flexible and does not contribute to the activation process. The activated form of DSR2 exists as tetramers and dimers, with the tetramers exhibiting more NADase activity. Overall, our results extend the current understanding of autoinhibition and activation of DSR2 immune proteins. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.5 MB | Display | ![]() |
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PDB format | ![]() | 1.3 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 39382 ![]() 39369 ![]() 39380 ![]() 39381 ![]() 39385 ![]() 39386 ![]() 39387 ![]() 39390 ![]() 39718 ![]() 60470 ![]() 8ykfC ![]() 8ylnC ![]() 8yltC ![]() 8z18C ![]() 8ztrC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 118635.789 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Protein | Mass: 13872.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-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
Component | Name: The DSR2-DSAD1 complex with DSAD1 on the same sides / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 289 K |
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Electron microscopy imaging
Microscopy | Model: FEI TITAN |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69487 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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