Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8
| العنوان: | Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8 |
|---|---|
| المؤلفون: | Yaming Zhang, Franklin L. Zhong, Chenrui Xu, Zhao Zhi Boo, Kim S. Robinson, Bruno Reversade, Daniel Eng Thiam Teo, Kenneth Lay, Jiawen Zhang, Graham D. Wright, John Soon Yew Lim, Eddie Yong Jun Tan, Kelvin Han Chung Chong, Wah Ing Goh, Qin Gong, Phuong Thao Huynh, Bin Wu |
| المساهمون: | ACS - Heart failure & arrhythmias, Reversade, Bruno, Gong, Q., Robinson, K., Xu, C., Huynh, P.T., Chong, K.H.C., Tan, E.Y.J., Zhang, J., Boo, Z.Z., Teo, D.E.T., Lay, K., Zhang, Y., Lim, J.S.Y., Goh, W.I., Wright, G., Zhong, F.L., Wu, B., School of Medicine |
| المصدر: | Nature communications, 12(1):188. Nature Publishing Group Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell biology, Inflammasomes, Biochemistry, Science, General Physics and Astronomy, NLR Proteins, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, Inflammasome, Protein filament, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Receptor, Adaptor Proteins, Signal Transducing, Inflammation, Mutation, Multidisciplinary, Chemistry, HEK 293 cells, Caspase 1, Cryoelectron Microscopy, Signal transducing adaptor protein, General Chemistry, Neoplasm Proteins, CARD Signaling Adaptor Proteins, Molecular Docking Simulation, 030104 developmental biology, HEK293 Cells, Cryoelectron microscopy, Signal transduction, Apoptosis Regulatory Proteins, Inflammasome complex, 030217 neurology & neurosurgery, medicine.drug, Signal Transduction |
| الوصف: | Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells—a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes. NLRP1 and CARD8 are two recently described sensor proteins for the human inflammasome complex. Here, the authors present the cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains, which reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. They further propose a two-step model for NLRP1 activation. |
| وصف الملف: | |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::971fea044a57af53224281deaea2a5a9Test https://pure.amc.nl/en/publications/structural-basis-for-distinct-inflammasome-complex-assembly-by-human-nlrp1-and-card8Test(f93492eb-c2e0-49e8-a33d-9316ae5981a5).html |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....971fea044a57af53224281deaea2a5a9 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |