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TitleHuman NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateSep 15, 2024
AuthorsJue Wang / Man Wu / Venkat G Magupalli / Peter D Dahlberg / Hao Wu / Grant J Jensen /
PubMed AbstractThe NLRP3 inflammasome is a multi-protein molecular machine that mediates inflammatory responses in innate immunity. Its dysregulation has been linked to a large number of human diseases. Using ...The NLRP3 inflammasome is a multi-protein molecular machine that mediates inflammatory responses in innate immunity. Its dysregulation has been linked to a large number of human diseases. Using cryogenic fluorescence-guided focused-ion-beam (cryo-FIB) milling and electron cryo-tomography (cryo-ET), we obtained 3-D images of the NLRP3 inflammasome at various stages of its activation at macromolecular resolution. The cryo-tomograms unexpectedly reveal dense condensates of the human macrophage NLRP3 inflammasome that form within and around the microtubule organizing center (MTOC). We also find that following activation, the trans-Golgi network disperses and 50-nm NLRP3-associated vesicles appear which likely ferry NLRP3 to the MTOC. At later time points after activation, the electron-dense condensates progressively solidify and the cells undergo pyroptosis with widespread damaged mitochondria and autophagasomal structures.
External linksbioRxiv / PubMed:39314395 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-75244: Cryo-tomogram of a patch-like NLRP3 inflammasome condensate at the MTOC
Method: EM (tomography)

EMDB-75245: Cryo-tomogram of a solid-like NLRP3 inflammasome condensate at the MTOC
Method: EM (tomography)

EMDB-75246: Cryo-tomogram of the MTOC in human THP-1 cells
Method: EM (tomography)

EMDB-75247: Cryo-tomogram of a matured NLRP3 inflammasome condensate at the MTOC
Method: EM (tomography)

EMDB-75248: Cryo-tomogram of the MTOC in LPS-treated human THP-1 cells
Method: EM (tomography)

EMDB-75249: Cryo-tomogram of NLRP3-associated vesicles residing at the Golgi following LPS treatment
Method: EM (tomography)

EMDB-75250: Patch-like NLRP3 inflammasome condensate formed above or below the MTOC
Method: EM (tomography)

Source
  • Human THP-1 cells (human)

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