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Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation

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dc.contributor.authorAngosto-Bazarra, Diego
dc.contributor.authorAlarcón-Vila, Cristina
dc.contributor.authorBaños, Maria C
dc.contributor.authorHafner-Bratkovič, Iva
dc.contributor.authorOliva, Baldomero
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.authorTapia Abellán, Ana
dc.contributor.departmentBioquímica y Biología Molecular B e Inmunología
dc.date.accessioned2025-01-20T12:53:16Z
dc.date.available2025-01-20T12:53:16Z
dc.date.issued2021-09-15
dc.description© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in Science Advances. To access the final edited and published work see https://doi.org/10.1126/sciadv.abf4468es
dc.description.abstractThe NLRP3 inflammasome is activated in response to a wide range of stimuli and drives diverse inflammatory diseases. The decrease of intracellular K+ concentration is a minimal upstream signal to most of the different NLRP3 activation models. Here we found that cellular K+ efflux induces a stable structural change in the inactive NLRP3 promoting an open conformation as a step preceding activation. This conformational change is facilitated by the presence of the specific NLRP3 FISNA domain and a unique flexible linker sequence between the PYD and FISNA domains. This linker is also important to facilitate the ensemble of NLRP3PYD into a seed structure for ASC oligomerization. The introduction of the NLRP3 PYD-linker-FISNA sequence into NLRP6 resulted in a chimeric receptor able to be activated by K+ efflux-specific NLRP3 activators and promoted an in vivo inflammatory response to uric acid crystals. Our results establish that the N-terminal sequence between PYD and NACHT domain of NLRP3 is key for inflammasome activation.es
dc.formatapplication/pdfes
dc.format.extent71es
dc.identifier.citationScience Advances, 2021, Vol. 7, Issue 38 : eabf4468
dc.identifier.doihttps://doi.org/10.1126/sciadv.abf4468
dc.identifier.issnElectronic: 2375-2548
dc.identifier.urihttp://hdl.handle.net/10201/148842
dc.languageenges
dc.publisherAmerican Association for the Advancement of Sciencees
dc.relationOrganismo: FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación. Convocatoria: Proyectos de investigación. Código: SAF2017-88276-R. Organismo: Fundación Séneca, Convocatoria: Proyectos de investigación. Códigos: 20859/PI/18, 21081/PDC/19 y 0003/COVI/20. Organismo: European Research Council. Convocatoria: ERC-2013-CoG. Código: 614578. Organismo: European Research Council. Convocatoria: ERC-2019-PoC. Código: 899636.es
dc.relation.publisherversionhttps://www.science.org/doi/full/10.1126/sciadv.abf4468?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.orges
dc.rightsinfo:eu-repo/semantics/embargoedAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectInflammasomees
dc.subjectInflammationes
dc.subjectNLRP3es
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísicaes
dc.titleSensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication0ef289d2-ad85-4d81-a66c-82879daf26a9
relation.isAuthorOfPublication.latestForDiscovery547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
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