Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I

Alessia Andreola, Vittorio Bellotti, Sofia Giorgetti, Palma Mangione, Laura Obici, Monica Stoppini, Jaume Torres, Enrico Monzani, Giampaolo Merlini, Margaret Sunde

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Abstract

The N-terminal portion of apolipoprotein A-I corresponding to the first 93 residues has been identified as the main component of apolipoprotein A-I fibrils in a form of systemic amyloidosis. We have been able to characterize the process of conformational switching and fibrillogenesis in this fragment of apolipoprotein A-I purified directly from ex vivo amyloid material. The peptide exists in an unstructured form in aqueous solution at neutral pH. The acidification of the solution provokes a collapse into a more compact, intermediate state and the transient appearance of a helical conformation that rapidly converts to a stable, mainly β-structure in the fibrils. The transition from helical to sheet structure occurs concomitantly with peptide self-aggregation, and fibrils are detected after 72 h. The α-helical conformation is induced by the addition of trifluoroethanol and phospholipids. Interaction of the amyloidogenic polypeptide with phospholipids prevents the switching from helical to β-sheet form and inhibits fibril formation. The secondary structure propensity of the apolipoprotein A-I fragment appears poised between helix and the β-sheet. These findings reinforce the idea of a delicate balance between natively stabilizing interactions and fatally stabilizing interactions and stress the importance of cellular localization and environment in the maintenance of protein conformation.

Original languageEnglish
Pages (from-to)2444-2451
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number4
DOIs
Publication statusPublished - Jan 24 2003

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Apolipoprotein A-I
Conformations
Peptides
Phospholipids
Trifluoroethanol
Protein Conformation
Acidification
Amyloidosis
Amyloid
Agglomeration
Maintenance
Proteins

ASJC Scopus subject areas

  • Biochemistry

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Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I. / Andreola, Alessia; Bellotti, Vittorio; Giorgetti, Sofia; Mangione, Palma; Obici, Laura; Stoppini, Monica; Torres, Jaume; Monzani, Enrico; Merlini, Giampaolo; Sunde, Margaret.

In: Journal of Biological Chemistry, Vol. 278, No. 4, 24.01.2003, p. 2444-2451.

Research output: Contribution to journalArticle

Andreola, A, Bellotti, V, Giorgetti, S, Mangione, P, Obici, L, Stoppini, M, Torres, J, Monzani, E, Merlini, G & Sunde, M 2003, 'Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I', Journal of Biological Chemistry, vol. 278, no. 4, pp. 2444-2451. https://doi.org/10.1074/jbc.M204801200
Andreola, Alessia ; Bellotti, Vittorio ; Giorgetti, Sofia ; Mangione, Palma ; Obici, Laura ; Stoppini, Monica ; Torres, Jaume ; Monzani, Enrico ; Merlini, Giampaolo ; Sunde, Margaret. / Conformational switching and fibrillogenesis in the amyloidogenic fragment of apolipoprotein A-I. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 4. pp. 2444-2451.
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