Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes
Pathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the...
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| Language: | English |
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Nature Publishing Group
2021-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-20320-y |
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doaj-0e61c5714aba4c07951365c347f3e5232021-01-10T12:18:11ZengNature Publishing GroupNature Communications2041-17232021-01-0112111310.1038/s41467-020-20320-yMechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomesL. Robert Hollingsworth0Liron David1Yang Li2Andrew R. Griswold3Jianbin Ruan4Humayun Sharif5Pietro Fontana6Elizabeth L. Orth-He7Tian-Min Fu8Daniel A. Bachovchin9Hao Wu10Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolDepartment of Biophysics, University of Texas Southwestern Medical CenterWeill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD ProgramDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer CenterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolPharmacology Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer CenterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical SchoolPathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the ASC−caspase-1 octamer structure, which together with in vitro and cell based assays provide further insights into the architecture and specificity of the active NLRP1 and CARD8 inflammasomes.https://doi.org/10.1038/s41467-020-20320-y |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes Nature Communications |
| author_facet |
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 |
| author_sort |
L. Robert Hollingsworth |
| title |
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes |
| title_short |
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes |
| title_full |
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes |
| title_fullStr |
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes |
| title_full_unstemmed |
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes |
| title_sort |
mechanism of filament formation in upa-promoted card8 and nlrp1 inflammasomes |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2021-01-01 |
| description |
Pathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the ASC−caspase-1 octamer structure, which together with in vitro and cell based assays provide further insights into the architecture and specificity of the active NLRP1 and CARD8 inflammasomes. |
| url |
https://doi.org/10.1038/s41467-020-20320-y |
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