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Yorodumi- EMDB-29498: Cryo-EM structure of full-length human NLRC4 inflammasome with C1... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29498 | |||||||||
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Title | Cryo-EM structure of full-length human NLRC4 inflammasome with C12 symmetry | |||||||||
Map data | Map of full-length NLRC4 inflammasome with C12 symmetry focused on three consecutive protomers | |||||||||
Sample |
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Keywords | NLRC4 / NAIP / Inflammasome / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information The IPAF inflammasome / IPAF inflammasome complex / icosanoid biosynthetic process / canonical inflammasome complex / positive regulation of protein processing / caspase binding / activation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response ...The IPAF inflammasome / IPAF inflammasome complex / icosanoid biosynthetic process / canonical inflammasome complex / positive regulation of protein processing / caspase binding / activation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / endopeptidase activator activity / detection of bacterium / activation of innate immune response / positive regulation of interleukin-1 beta production / protein homooligomerization / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of NF-kappaB transcription factor activity / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / intracellular membrane-bounded organelle / innate immune response / apoptotic process / magnesium ion binding / protein homodimerization activity / ATP binding / identical protein binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.46 Å | |||||||||
Authors | Matico RE / Yu X / Miller R / Somani S / Ricketts MD / Kumar N / Steele RA / Medley Q / Berger S / Faustin B / Sharma S | |||||||||
Funding support | 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural basis of the human NAIP/NLRC4 inflammasome assembly and pathogen sensing. Authors: Rosalie E Matico / Xiaodi Yu / Robyn Miller / Sandeep Somani / M Daniel Ricketts / Nikit Kumar / Ruth A Steele / Quintus Medley / Scott Berger / Benjamin Faustin / Sujata Sharma / Abstract: The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in ...The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in response to cell stress during sterile chronic inflammation. Despite its major role in instigating the subsequent host immune response, a more complete understanding of the molecular events in the formation of the NLRC4 inflammasome in humans is lacking. Here we identify Bacillus thailandensis type III secretion system needle protein (Needle) as a potent trigger of the human NLR family apoptosis inhibitory protein (NAIP)/NLRC4 inflammasome complex formation and determine its structural features by cryogenic electron microscopy. We also provide a detailed understanding of how type III secretion system pathogen components are sensed by human NAIP to form a cascade of NLRC4 protomer through a critical lasso-like motif, a 'lock-key' activation model and large structural rearrangement, ultimately forming the full human NLRC4 inflammasome. These results shed light on key regulatory mechanisms specific to the NLRC4 inflammasome assembly, and the innate immune modalities of pathogen sensing in humans. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29498.map.gz | 398.4 MB | EMDB map data format | |
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Header (meta data) | emd-29498-v30.xml emd-29498.xml | 21 KB 21 KB | Display Display | EMDB header |
Images | emd_29498.png | 47.7 KB | ||
Filedesc metadata | emd-29498.cif.gz | 6 KB | ||
Others | emd_29498_additional_1.map.gz emd_29498_additional_2.map.gz emd_29498_additional_3.map.gz emd_29498_half_map_1.map.gz emd_29498_half_map_2.map.gz | 397.2 MB 390.9 MB 390.9 MB 391.7 MB 391.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29498 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29498 | HTTPS FTP |
-Validation report
Summary document | emd_29498_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_29498_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_29498_validation.xml.gz | 18 KB | Display | |
Data in CIF | emd_29498_validation.cif.gz | 21.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29498 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29498 | HTTPS FTP |
-Related structure data
Related structure data | 8fw9MC 8fvuC 8fw2C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_29498.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry focused on three consecutive protomers | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.948 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Map of full-length NLRC4 inflammasome with C12 symmetry
File | emd_29498_additional_1.map | ||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Map of full-length NLRC4 inflammasome with C12 symmetry
File | emd_29498_additional_2.map | ||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Map of full-length NLRC4 inflammasome with C12 symmetry
File | emd_29498_additional_3.map | ||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Map of full-length NLRC4 inflammasome with C12 symmetry...
File | emd_29498_half_map_1.map | ||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry focused on three consecutive protomers | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Map of full-length NLRC4 inflammasome with C12 symmetry...
File | emd_29498_half_map_2.map | ||||||||||||
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Annotation | Map of full-length NLRC4 inflammasome with C12 symmetry focused on three consecutive protomers | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : the complex of Needle, human NAIP and NLRC4
Entire | Name: the complex of Needle, human NAIP and NLRC4 |
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Components |
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-Supramolecule #1: the complex of Needle, human NAIP and NLRC4
Supramolecule | Name: the complex of Needle, human NAIP and NLRC4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: NLR family CARD domain-containing protein 4
Macromolecule | Name: NLR family CARD domain-containing protein 4 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 117.027656 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: AEYCFNMNFI KDNSRALIQR MGMTVIKQIT DDLFVWNVLN REEVNIICCE KVEQDAARGI IHMILKKGSE SCNLFLKSLK EWNYPLFQD LNGQSLFHQT SEGDLDDLAQ DLKDLYHTPS FLNFYPLGED IDIIFNLKST FTEPVLWRKD QHHHRVEQLT L NGLLQALQ ...String: AEYCFNMNFI KDNSRALIQR MGMTVIKQIT DDLFVWNVLN REEVNIICCE KVEQDAARGI IHMILKKGSE SCNLFLKSLK EWNYPLFQD LNGQSLFHQT SEGDLDDLAQ DLKDLYHTPS FLNFYPLGED IDIIFNLKST FTEPVLWRKD QHHHRVEQLT L NGLLQALQ SPCIIEGESG KGKSTLLQRI AMLWGSGKCK ALTKFKFVFF LRLSRAQGGL FETLCDQLLD IPGTIRKQTF MA MLLKLRQ RVLFLLDGYN EFKPQNCPEI EALIKENHRF KNMVIVTTTT ECLRHIRQFG ALTAEVGDMT EDSAQALIRE VLI KELAEG LLLQIQKSRC LRNLMKTPLF VVITCAIQMG ESEFHSHTQT TLFHTFYDLL IQKNKHKHKG VAASDFIRSL DHCG DLALE GVFSHKFDFE LQDVSSVNED VLLTTGLLCK YTAQRFKPKY KFFHKSFQEY TAGRRLSSLL TSHEPEEVTK GNGYL QKMV SISDITSTYS SLLRYTCGSS VEATRAVMKH LAAVYQHGCL LGLSIAKRPL WRQESLQSVK NTTEQEILKA ININSF VEC GIHLYQESTS KSALSQEFEA FFQGKSLYIN SGNIPDYLFD FFEHLPNCAS ALDFIKLDFY GGAMASWEKA AEDTGGI HM EEAPETYIPS RAVSLFFNWK QEFRTLEVTL RDFSKLNKQD IRYLGKIFSS ATSLRLQIKR CAGVAGSLSL VLSTCKNI Y SLMVEASPLT IEDERHITSV TNLKTLSIHD LQNQRLPGGL TDSLGNLKNL TKLIMDNIKM NEEDAIKLAE GLKNLKKMC LFHLTHLSDI GEGMDYIVKS LSSEPCDLEE IQLVSCCLSA NAVKILAQNL HNLVKLSILD LSENYLEKDG NEALHELIDR MNVLEQLTA LMLPWGCDVQ GSLSSLLKHL EEVPQLVKLG LKNWRLTDTE IRILGAFFGK NPLKNFQQLN LAGNRVSSDG W LAFMGVFE NLKQLVFFDF STKEFLPDPA LVRKLSQVLS KLTFLQEARL VGWQFDDDDL SVITGAFKLV TA UniProtKB: NLR family CARD domain-containing protein 4 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.46 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 21406 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |