CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.

The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many yea...

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Autores principales:	Andrea D'Osualdo, Christian X Weichenberger, Roland N Wagner, Adam Godzik, John Wooley, John C Reed
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/58570e84f44541c89c521a4dd5f68504
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spelling	oai:doaj.org-article:58570e84f44541c89c521a4dd5f685042021-11-18T07:34:44ZCARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.1932-620310.1371/journal.pone.0027396https://doaj.org/article/58570e84f44541c89c521a4dd5f685042011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22087307/?tool=EBIhttps://doaj.org/toc/1932-6203The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed that the second serine of the SF/S motif is required for CARD8 and NLRP1 autoproteolysis. Furthermore, we discovered an important function for conserved glutamic acid and histidine residues, located in proximity of the cleavage site in regulating the autoprocessing efficiency. Altogether, these results identify a function for the FIIND and show that CARD8 and NLRP1 are ZU5-UPA domain-containing autoproteolytic proteins, thus suggesting a novel mechanism for regulating innate immune responses.Andrea D'OsualdoChristian X WeichenbergerRoland N WagnerAdam GodzikJohn WooleyJohn C ReedPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27396 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea D'Osualdo Christian X Weichenberger Roland N Wagner Adam Godzik John Wooley John C Reed CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
description	The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed that the second serine of the SF/S motif is required for CARD8 and NLRP1 autoproteolysis. Furthermore, we discovered an important function for conserved glutamic acid and histidine residues, located in proximity of the cleavage site in regulating the autoprocessing efficiency. Altogether, these results identify a function for the FIIND and show that CARD8 and NLRP1 are ZU5-UPA domain-containing autoproteolytic proteins, thus suggesting a novel mechanism for regulating innate immune responses.
format	article
author	Andrea D'Osualdo Christian X Weichenberger Roland N Wagner Adam Godzik John Wooley John C Reed
author_facet	Andrea D'Osualdo Christian X Weichenberger Roland N Wagner Adam Godzik John Wooley John C Reed
author_sort	Andrea D'Osualdo
title	CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
title_short	CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
title_full	CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
title_fullStr	CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
title_full_unstemmed	CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.
title_sort	card8 and nlrp1 undergo autoproteolytic processing through a zu5-like domain.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/58570e84f44541c89c521a4dd5f68504
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CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.

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