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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-5830 | |||||||||
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Title | Unified assembly mechanism of ASC-dependent inflammasomes | |||||||||
![]() | Reconstruction of PYD filament | |||||||||
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![]() | helical polymer / variable twist / apoptosis / death domain | |||||||||
Function / homology | ![]() Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / myeloid dendritic cell activation / IkappaB kinase complex / The AIM2 inflammasome / AIM2 inflammasome complex ...Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / myeloid dendritic cell activation / IkappaB kinase complex / The AIM2 inflammasome / AIM2 inflammasome complex / macropinocytosis / icosanoid biosynthetic process / interleukin-6 receptor binding / NLRP1 inflammasome complex / canonical inflammasome complex / NLRP3 inflammasome complex assembly / positive regulation of adaptive immune response / NLRP3 inflammasome complex / BMP receptor binding / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / osmosensory signaling pathway / CLEC7A/inflammasome pathway / positive regulation of cysteine-type endopeptidase activity / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of macrophage cytokine production / pattern recognition receptor signaling pathway / positive regulation of actin filament polymerization / negative regulation of NF-kappaB transcription factor activity / tropomyosin binding / positive regulation of activated T cell proliferation / pyroptotic inflammatory response / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of release of cytochrome c from mitochondria / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of interleukin-10 production / The NLRP3 inflammasome / intrinsic apoptotic signaling pathway by p53 class mediator / cellular response to interleukin-1 / negative regulation of cytokine production involved in inflammatory response / positive regulation of T cell migration / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / negative regulation of canonical NF-kappaB signal transduction / positive regulation of phagocytosis / positive regulation of defense response to virus by host / tumor necrosis factor-mediated signaling pathway / activation of innate immune response / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / positive regulation of JNK cascade / regulation of protein stability / protein homooligomerization / positive regulation of DNA-binding transcription factor activity / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of interleukin-6 production / positive regulation of type II interferon production / activation of cysteine-type endopeptidase activity involved in apoptotic process / SARS-CoV-1 activates/modulates innate immune responses / azurophil granule lumen / positive regulation of tumor necrosis factor production / positive regulation of T cell activation / cellular response to tumor necrosis factor / positive regulation of NF-kappaB transcription factor activity / protease binding / cellular response to lipopolysaccharide / secretory granule lumen / defense response to virus / defense response to Gram-negative bacterium / transmembrane transporter binding / microtubule / positive regulation of ERK1 and ERK2 cascade / protein dimerization activity / defense response to Gram-positive bacterium / positive regulation of apoptotic process / Golgi membrane / innate immune response / neuronal cell body / Neutrophil degranulation / apoptotic process / nucleolus / enzyme binding / signal transduction / endoplasmic reticulum / protein homodimerization activity / protein-containing complex / mitochondrion / extracellular region / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Lu A / Magupalli VG / Ruan J / Yin Q / Atianand MK / Vos M / Schroder GF / Fitzgerald KA / Wu H / Egelman EH | |||||||||
![]() | ![]() Title: Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Authors: Alvin Lu / Venkat Giri Magupalli / Jianbin Ruan / Qian Yin / Maninjay K Atianand / Matthijn R Vos / Gunnar F Schröder / Katherine A Fitzgerald / Hao Wu / Edward H Egelman / ![]() ![]() ![]() Abstract: Inflammasomes elicit host defense inside cells by activating caspase-1 for cytokine maturation and cell death. AIM2 and NLRP3 are representative sensor proteins in two major families of inflammasomes. ...Inflammasomes elicit host defense inside cells by activating caspase-1 for cytokine maturation and cell death. AIM2 and NLRP3 are representative sensor proteins in two major families of inflammasomes. The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain (PYD) interactions between sensors and ASC and through caspase activation and recruitment domain (CARD) interactions between ASC and caspase-1. We found that PYD and CARD both form filaments. Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation. Endogenous NLRP3 inflammasome is also filamentous. The cryoelectron microscopy structure of ASC(PYD) filament at near-atomic resolution provides a template for homo- and hetero-PYD/PYD associations, as confirmed by structure-guided mutagenesis. We propose that ASC-dependent inflammasomes in both families share a unified assembly mechanism that involves two successive steps of nucleation-induced polymerization. PAPERFLICK: | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 9.1 KB 9.1 KB | Display Display | ![]() |
Images | ![]() ![]() | 76.8 KB 5.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3j63MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Reconstruction of PYD filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : PYD domain from ASC
Entire | Name: PYD domain from ASC |
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Components |
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-Supramolecule #1000: PYD domain from ASC
Supramolecule | Name: PYD domain from ASC / type: sample / ID: 1000 / Oligomeric state: helical polymer / Number unique components: 1 |
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-Macromolecule #1: Apoptosis-associated speck-like protein containing a CARD
Macromolecule | Name: Apoptosis-associated speck-like protein containing a CARD type: protein_or_peptide / ID: 1 / Name.synonym: pyrin domain, death domain / Oligomeric state: helical polymer / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | helical array |
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Sample preparation
Grid | Details: over holes in lacey carbon grids, no support |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Date | Dec 20, 2012 |
Image recording | Category: CCD / Film or detector model: FEI FALCON II (4k x 4k) / Number real images: 400 / Average electron dose: 20 e/Å2 / Details: Integrating mode used |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Details | IHRSR |
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Final reconstruction | Applied symmetry - Helical parameters - Δz: 13.95 Å Applied symmetry - Helical parameters - Δ&Phi: 52.9 ° Applied symmetry - Helical parameters - Axial symmetry: C3 (3 fold cyclic) Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: OTHER / Software - Name: Spider, IHRSR |
CTF correction | Details: each image |