The tempered polymerization of human neuroserpin.

Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases...

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Autores principales:	Rosina Noto, Maria Grazia Santangelo, Stefano Ricagno, Maria Rosalia Mangione, Matteo Levantino, Margherita Pezzullo, Vincenzo Martorana, Antonio Cupane, Martino Bolognesi, Mauro Manno
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/006e9ff63bbb424697374b674fb907f4
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spelling	oai:doaj.org-article:006e9ff63bbb424697374b674fb907f42021-11-18T07:25:58ZThe tempered polymerization of human neuroserpin.1932-620310.1371/journal.pone.0032444https://doaj.org/article/006e9ff63bbb424697374b674fb907f42012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412873/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation.Rosina NotoMaria Grazia SantangeloStefano RicagnoMaria Rosalia MangioneMatteo LevantinoMargherita PezzulloVincenzo MartoranaAntonio CupaneMartino BolognesiMauro MannoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32444 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rosina Noto Maria Grazia Santangelo Stefano Ricagno Maria Rosalia Mangione Matteo Levantino Margherita Pezzullo Vincenzo Martorana Antonio Cupane Martino Bolognesi Mauro Manno The tempered polymerization of human neuroserpin.
description	Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation.
format	article
author	Rosina Noto Maria Grazia Santangelo Stefano Ricagno Maria Rosalia Mangione Matteo Levantino Margherita Pezzullo Vincenzo Martorana Antonio Cupane Martino Bolognesi Mauro Manno
author_facet	Rosina Noto Maria Grazia Santangelo Stefano Ricagno Maria Rosalia Mangione Matteo Levantino Margherita Pezzullo Vincenzo Martorana Antonio Cupane Martino Bolognesi Mauro Manno
author_sort	Rosina Noto
title	The tempered polymerization of human neuroserpin.
title_short	The tempered polymerization of human neuroserpin.
title_full	The tempered polymerization of human neuroserpin.
title_fullStr	The tempered polymerization of human neuroserpin.
title_full_unstemmed	The tempered polymerization of human neuroserpin.
title_sort	tempered polymerization of human neuroserpin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/006e9ff63bbb424697374b674fb907f4
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The tempered polymerization of human neuroserpin.

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