The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Cryo-EM structures of the active NLRP3 inflammasome disc
Open accessAbstract
We report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with NEK7 and ASC, and propose that the role of NEK7 is to transform NLRP3 into the active NLRP3 inflammasome disc. Inflammasomes are cytosolic innate immune complexes that activate caspase-1 following detection of pathogenic and endogenous dangers^ 1 – 5 , and NACHT-, leucine-rich repeat (LRR)- and pyrin domain (PYD)-containing protein 3 (NLRP3) is an inflammasome sensor of membrane damage highly important in regard to the induction of inflammation^ 2 , 6 , 7 . Here we report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with adenosine 5′-O-(3-thio)triphosphate, the centrosomal NIMA-related kinase 7 (NEK7) and the adaptor protein ASC, which recruits caspase-1. In these NLRP3–NEK7–ASC complexes, the central NACHT domain of NLRP3 assumes an ATP-bound conformation in which two of its subdomains rotate by about 85° relative to the ADP-bound inactive conformation^ 8 – 12 . The fish-specific NACHT-associated domain conserved in NLRP3 but absent in most NLRPs^ 13 becomes ordered in its key regions to stabilize the active NACHT conformation and mediate most interactions in the disc. Mutations on these interactions compromise NLRP3-mediated caspase-1 activation. The N-terminal PYDs from all NLRP3 subunits combine to form a PYD filament that recruits ASC PYD to elicit downstream signalling. Surprisingly, the C-terminal LRR domain and the LRR-bound NEK7 do not participate in disc interfaces. Together with previous structures of an inactive NLRP3 cage in which LRR–LRR interactions play an important role^ 8 – 11 , we propose that the role of NEK7 is to break the inactive cage to transform NLRP3 into the active NLRP3 inflammasome disc.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination
Punjani, A., Rubinstein, J. L., Fleet, D. J., & Brubaker, M. A. (2017) · Nature Methods · doi:10.1038/nmeth.4169 · Cited by 11,626
Inference of Macromolecular Assemblies from Crystalline State
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 9,984
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S. Q., Palovcak, E., Armache, J.-P., Verba, K. A., Cheng, Y., & Agard, D. A. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,777
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
Shi, J., Zhao, Y., Wang, K., Shi, X., Wang, Y., Huang, H., Zhuang, Y., Cai, T., Wang, F., & Shao, F. (2015) · Nature · doi:10.1038/nature15514 · Cited by 6,659
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
UCSF ChimeraX: Meeting modern challenges in visualization and analysis
Goddard, T. D., Huang, C. C., Meng, E. C., Pettersen, E. F., Couch, G. S., Morris, J. H., & Ferrin, T. E. (2018) · Protein Science · doi:10.1002/pro.3235 · Cited by 5,267
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
Rohou, A., & Grigorieff, N. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.08.008 · Cited by 4,913
Cited by
The NLRP3 inflammasome: contributions to inflammation-related diseases
Chen, Y., Ye, X., Escames, G., Lei, W., Zhang, X., Li, M., Jing, T., Yao, Y., Qiu, Z., Wang, Z., et al. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00462-9 · Cited by 492
A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases
Barnett, K. C., Li, S., Liang, K., & Ting, J. P.-Y. (2023) · Cell · doi:10.1016/j.cell.2023.04.025 · Cited by 458
Structural basis for the oligomerization-facilitated NLRP3 activation
Yu, X., Matico, R. E., Miller, R., Chauhan, D., Van Schoubroeck, B., Grauwen, K., Suarez, J., Pietrak, B., Haloi, N., Yin, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45396-8 · Cited by 78
A cereblon-based glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner
Sylvain, A., Stoehr, N., Ma, F., Cernijenko, A., Schröder, M., Khoshouei, M., Vogelsanger, M., Schoenboerner, M., Burke, A., Rao, P., et al. (2025) · Cell Chemical Biology · doi:10.1016/j.chembiol.2025.06.005 · Cited by 23
Filamentation activates bacterial Avs5 antiviral protein
Wang, Y., Tian, Y., Yang, X., Yu, F., & Zheng, J. (2025) · Nature Communications · doi:10.1038/s41467-025-57732-7 · Cited by 18
Metadata
- Authors
- Xiao, L., Magupalli, V. G., & Wu, H.
- Venue
- Nature
- Published
- 2022-11-28
- Volume
- 613
- Issue
- 7944
- Pages
- 595-600
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4310157187
- Cited by
- 312
- References
- 61
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Cryo-EM structures of the active NLRP3 inflammasome disc. https://app.cochat.ai/papers/10.1038/s41586-022-05570-8
- The paper
- Xiao, L., Magupalli, V. G., & Wu, H. (2023). Cryo-EM structures of the active NLRP3 inflammasome disc. Nature. https://doi.org/10.1038/s41586-022-05570-8
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
