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Open data
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Basic information
Entry | Database: PDB / ID: 6mb2 | ||||||
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Title | Cryo-EM structure of the PYD filament of AIM2 | ||||||
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![]() | IMMUNE SYSTEM / Filament / higher order / innate immunity / inflammasome | ||||||
Function / homology | ![]() pyroptosome complex assembly / AIM2 inflammasome complex assembly / The AIM2 inflammasome / cysteine-type endopeptidase activator activity / regulation of behavior / AIM2 inflammasome complex / Cytosolic sensors of pathogen-associated DNA / positive regulation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / pattern recognition receptor activity ...pyroptosome complex assembly / AIM2 inflammasome complex assembly / The AIM2 inflammasome / cysteine-type endopeptidase activator activity / regulation of behavior / AIM2 inflammasome complex / Cytosolic sensors of pathogen-associated DNA / positive regulation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / pattern recognition receptor activity / negative regulation of NF-kappaB transcription factor activity / pyroptotic inflammatory response / T cell homeostasis / cellular response to interferon-beta / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / signaling adaptor activity / positive regulation of defense response to virus by host / tumor necrosis factor-mediated signaling pathway / activation of innate immune response / bioluminescence / positive regulation of interleukin-1 beta production / generation of precursor metabolites and energy / brain development / neuron cellular homeostasis / positive regulation of inflammatory response / cellular response to xenobiotic stimulus / site of double-strand break / positive regulation of NF-kappaB transcription factor activity / double-stranded DNA binding / defense response to virus / inflammatory response / immune response / innate immune response / DNA damage response / mitochondrion / nucleoplasm / identical protein binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 5 Å | ||||||
![]() | Lu, A. / Li, Y. / Wu, H. | ||||||
![]() | ![]() Title: Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2. Authors: Alvin Lu / Yang Li / Qian Yin / Jianbin Ruan / Xiong Yu / Edward Egelman / Hao Wu / ![]() Abstract: Absent in melanoma 2 (AIM2) is an essential cytosolic double-stranded DNA receptor that assembles with the adaptor, apoptosis-associated speck-like protein containing a caspase recruitment domain ...Absent in melanoma 2 (AIM2) is an essential cytosolic double-stranded DNA receptor that assembles with the adaptor, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 to form the AIM2 inflammasome, which leads to proteolytic maturation of cytokines and pyroptotic cell death. AIM2 contains an N-terminal Pyrin domain (PYD) that interacts with ASC through PYD/PYD interactions and nucleates ASC filament formation. To elucidate the molecular basis of AIM2-induced ASC polymerization, we generated AIM2 filaments fused to green fluorescent protein (GFP) and determined its cryo-electron microscopic (cryo-EM) structure. The map showed distinct definition of helices, allowing fitting of the crystal structure. Surprisingly, the GFP-AIM2 filament is a 1-start helix with helical parameters distinct from those of the 3-start ASC filament. However, despite the apparent symmetry difference, helical net and detailed interface analyses reveal minimal changes in subunit packing. GFP-AIM2 nucleated ASC filament formation in comparable efficiency as untagged AIM2, suggesting assembly plasticity in both AIM2 and ASC. The DNA-binding domain of AIM2 is able to form AIM2/DNA filaments, within which the AIM2 is brought into proximity to template ASC filament assembly. Because ASC is able to interact with many PYD-containing receptors for the formation of inflammasomes, the observed structural plasticity may be critically important for this versatility in the PYD/PYD interactions. | ||||||
History |
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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 | ![]() | 910.6 KB | Display | ![]() |
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PDB format | ![]() | 775.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 131.6 KB | Display | |
Data in CIF | ![]() | 177.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9064MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Symmetry | Helical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 15 / Rise per n subunits: 6 Å / Rotation per n subunits: 138.9 °) |
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Components
#1: Protein | Mass: 10839.629 Da / Num. of mol.: 15 / Fragment: PYD (UNP residues 1-93) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 25924.553 Da / Num. of mol.: 15 / Fragment: UNP residues 2-229 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: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: PYD of AIM2 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
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: 50 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.8.2_1309 / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 138.9 ° / Axial rise/subunit: 6 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 54973 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 5→150 Å / SU ML: 1.77 / σ(F): 0.76 / Phase error: 64.53 / Stereochemistry target values: MLHL
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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LS refinement shell |
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