Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils (Articolo in rivista)

Type
Label
  • Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Paolo Paoli; Francesca Sbrana; Bruno Tiribilli; Anna Caselli;Barbara Pantera; Paolo Cirri; Alina De Donatis; Lucia Formigli; Daniele Nosi; Giampaolo Manao; Guido Camici; Giampietro Ramponi (2010)
    Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils
    in Journal of Molecular Biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Paolo Paoli; Francesca Sbrana; Bruno Tiribilli; Anna Caselli;Barbara Pantera; Paolo Cirri; Alina De Donatis; Lucia Formigli; Daniele Nosi; Giampaolo Manao; Guido Camici; Giampietro Ramponi (literal)
Pagina inizio
  • 889 (literal)
Pagina fine
  • 907 (literal)
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  • 400 (literal)
Rivista
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  • fasc. (4). Elsevier. (literal)
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  • 18 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • Dipartimento di Scienze Biochimiche, Università di Firenze, Viale Morgagni 50, 50134 Firenze, Italy Centro per lo Studio delle Dinamiche Complesse, Dipartimento di Fisica, Università degli Studi di Firenze, via Sansone 1, 50019, Sesto F.no, Firenze, Italy CNR-ISC, Firenze - Sesto Fiorentino, Dipartimento di Anatomia, Istologia e Medicina Legale, Università degli Studi di Firenze, Viale Morgagni 85, 50134 Firenze, Italy Dipartimento di Scienze Biochimiche, Univ. degli Studi di Firenze, Viale Morgagni 50, 50134 Firenze Center of Excellence for Res., Transfer of Res. and High Education for the Development of Novel Therapies (DENOthe), Univ. degli Studi di Firenze, Dipartimento di Scienze Biochimiche, Univ. degli Studi di Firenze, Viale Morgagni 50, 50134 Firenze (literal)
Titolo
  • Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils (literal)
Abstract
  • Previous works reported that a mild increase in homocysteine level is a risk factor for cardiovascular and neurodegenerative diseases in humans. Homocysteine thiolactone is a cyclic thioester, most of which is produced by an error-editing function of methionyl-tRNA synthetase, causing in vivo post-translational protein modifications by reacting with the var epsilon-amino group of lysine residues. In cells, the rate of homocysteine thiolactone synthesis is strictly dependent on the levels of the precursor metabolite, homocysteine. In this work, using bovine serum albumin as a model, we investigated the impact of N-homocysteinylation on protein conformation as well as its cellular actions. Previous works demonstrated that protein N-homocysteinylation causes enzyme inactivation, protein aggregation, and precipitation. In addition, in the last few years, several pieces of evidence have indicated that protein unfolding and aggregation are crucial events leading to the formation of amyloid fibrils associated with a wide range of human pathologies. For the first time, our results reveal how the low level of protein N-homocysteinylation can induce mild conformational changes leading to the formation of native-like aggregates evolving over time, producing amyloid-like structures. Taking into account the fact that in humans about 70% of circulating homocysteine is N-linked to blood proteins such as serum albumin and hemoglobin, the results reported in this article could have pathophysiological relevance and could contribute to clarify the mechanisms underlying some pathological consequences described in patients affected by hyperhomocysteinemia. (literal)
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