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NLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathway

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dc.contributor.authorHafner-Bratkovic, Iva
dc.contributor.authorSusjan, Petra
dc.contributor.authorLainscek, Dusko
dc.contributor.authorCerovic, Kosta
dc.contributor.authorKadunc, Lucija
dc.contributor.authorAngosto-Bazarra, Diego
dc.contributor.authorJerala, Roman
dc.contributor.authorTapia Abellán, Ana
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.departmentBioquímica y Biología Molecular B e Inmunología
dc.date.accessioned2024-01-30T11:18:40Z
dc.date.available2024-01-30T11:18:40Z
dc.date.issued2018
dc.description©2018. 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, version of a Published Work that appeared in final form in Nature Communications. To access the final edited and published work see https://doi.org/10.1038/s41467-018-07573-4
dc.description.abstractNLRP3 is a cytosolic sensor triggered by different pathogen- and self-derived signals that plays a central role in a variety of pathological conditions, including sterile inflammation. The leucine- rich repeat domain is present in several innate immune receptors, where it is frequently responsible for sensing danger signals and regulation of activation. We show by reconstitution of truncated and chimeric variants into NLRP3-/- macrophages that the leucine-rich repeat domain is dispensable for activation and self-regulation of NLRP3 by several different triggers. The pyrin domain on the other hand is required to maintain NLRP3 in the inactive conformation. A fully responsive minimal NLRP3 truncation variant reconstituted peritonitis in NLRP3-/- mice. We demonstrate that in contrast to pathogen-activated NLRC4, the constitutively active NLRP3 molecule cannot engage wild-type NLRP3 molecules in a self-catalytic oligomerization. This lack of signal amplification is likely a protective mechanism to decrease sensitivity to endogenous triggers to impede autoinflammation.es
dc.formatapplication/pdfes
dc.format.extent48es
dc.identifier.citationNature Communications, volumen 9, nº 1, año 2018, número de artículo 5182 (18 páginas).
dc.identifier.doihttps://doi.org/10.1038/s41467-018-07573-4
dc.identifier.urihttp://hdl.handle.net/10201/138131
dc.languageenges
dc.publisherNaturees
dc.relationSlovenian Research Agency (J3-5503, J3-6791), Instituto Salud Carlos III–Fondo Europeo de Desarrollo Regional (PI13/00174), European Research Council (ERC-2013- CoG 614578), COST Action BM-1406.es
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-018-07573-4es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectInterleukin-1βes
dc.subjectMacrophagees
dc.subjectInflammasomees
dc.subjectNLRP3es
dc.subjectInflammationes
dc.subject.otherCDU::6 - Ciencias aplicadases
dc.titleNLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathwayes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication0ef289d2-ad85-4d81-a66c-82879daf26a9
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication.latestForDiscovery0ef289d2-ad85-4d81-a66c-82879daf26a9
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