Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes.
Journal, issue, pages	Nat Commun, Vol. 12, Issue 1, Page 189, Year 2021
Publish date	Jan 8, 2021
Authors	L Robert Hollingsworth / Liron David / Yang Li / Andrew R Griswold / Jianbin Ruan / Humayun Sharif / Pietro Fontana / Elizabeth L Orth-He / Tian-Min Fu / Daniel A Bachovchin / Hao Wu /
PubMed Abstract	NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation ...NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1 filament dimerize with additional exterior CARDs, which roughly doubles its thickness and is unique among all known CARD filaments. Finally, we engineer and determine the structure of an ASC-caspase-1 octamer, which suggests that ASC uses opposing surfaces for NLRP1, versus caspase-1, recruitment. Together these structures capture the architecture and specificity of the active NLRP1 and CARD8 inflammasomes in addition to key heteromeric CARD-CARD interactions governing inflammasome signalling.
External links	Nat Commun / PubMed:33420033 / PubMed Central
Methods	EM (helical sym.) / EM (single particle)
Resolution	3.54 - 5.0 Å
Structure data	22219 6xkj EMDB-22219, PDB-6xkj: Cryo-EM structure of CARD8-CARD filament Method: EM (helical sym.) / Resolution: 3.54 Å 22220 6xkk EMDB-22220, PDB-6xkk: Cryo-EM structure of the NLRP1-CARD filament Method: EM (helical sym.) / Resolution: 3.72 Å 22233 7keu EMDB-22233: Cryo-EM structure of ASC-Caspase1 Octamer PDB-7keu: Cryo-EM structure of the Caspase-1-CARD:ASC-CARD octamer Method: EM (single particle) / Resolution: 5.0 Å
Source	homo sapiens (human)
Keywords	IMMUNE SYSTEM / Filament / inflammasome / signaling / UPA / FIIND / CARD / NLRP1 / ASC / Apoptosis-associated speck-like protein containing a CARD / PYCARD / caspase-1 / cryo-EM / helical filament / octamer