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Recent studies have elucidated its transition from a closed cage to an activated disk-like inflammasome, but the intermediate activation mechanism remains elusive. Here we report the cryo-electron microscopy structure of NLRP3, which forms an open octamer and undergoes a\u2009~\u200990\u00b0 hinge rotation at the NACHT domain. Mutations on open octamer\u2019s interfaces reduce IL-1\u03b2 signaling, highlighting its essential role in NLRP3 activation\/inflammasome assembly. The centrosomal NIMA-related kinase\u20097 (NEK7) disrupts large NLRP3 oligomers and forms NEK7\/NLRP3 monomers\/dimers which is a critical step preceding the assembly of the disk-like inflammasome. These data demonstrate an oligomeric cooperative activation of NLRP3 and provide insight into its inflammasome assembly mechanism.<\/jats:p>","DOI":"10.1038\/s41467-024-45396-8","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T13:02:44Z","timestamp":1707310964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Structural basis for the oligomerization-facilitated NLRP3 activation"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-0646","authenticated-orcid":false,"given":"Xiaodi","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie E.","family":"Matico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Van Schoubroeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolien","family":"Grauwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Suarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Pietrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3542-333X","authenticated-orcid":false,"given":"Nandan","family":"Haloi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4801-1644","authenticated-orcid":false,"given":"Gary John","family":"Tresadern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Perez-Benito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-2794","authenticated-orcid":false,"given":"Erik","family":"Lindahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Bottelbergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Oehlrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Van Opdenbosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-2939","authenticated-orcid":false,"given":"Sujata","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"45396_CR1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.4049\/jimmunol.1500530","volume":"195","author":"T Eigenbrod","year":"2015","unstructured":"Eigenbrod, T. & Dalpke, A. 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