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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032444&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-006e9ff63bbb424697374b674fb907f4 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-006e9ff63bbb424697374b674fb907f42025-08-20T03:25:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3244410.1371/journal.pone.0032444The tempered polymerization of human neuroserpin.Rosina NotoMaria Grazia SantangeloStefano RicagnoMaria Rosalia MangioneMatteo LevantinoMargherita PezzulloVincenzo MartoranaAntonio CupaneMartino BolognesiMauro MannoNeuroserpin, 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032444&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | The tempered polymerization of human neuroserpin. |
| title_sort | tempered polymerization of human neuroserpin |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032444&type=printable |
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