Recombinant amyloidogenic domain of ApoA-I: Analysis of its fibrillogenic potential
- Istituto di Biostrutture e Bioimmagini, CNR, Naples 80134 (Italy)
- Dipartimento di Biologia Strutturale e Funzionale, Universita di Napoli Federico II, Complesso Universitario di Monte S. Angelo, via Cinthia 4, Naples 80126 (Italy)
- Dipartimento di Biochimica, Universita di Pavia, Pavia 27100 (Italy)
- CEINGE Biotecnologie Avanzate, Naples 80131 (Italy)
- Dipartimento di Fisica, Universita di Genova, Genova 16146 (Italy)
- Department of Chemistry, University of Cambridge, Cambridge CB2 IEW (United Kingdom)
A variety of amyloid diseases are associated with fibrillar aggregates from N-terminal fragments of ApoA-I generated through a largely unexplored multi-step process. The understanding of the molecular mechanism is impaired by the lack of suitable amounts of the fibrillogenic polypeptides that could not be produced by recombinant methods so far. We report the production and the conformational analysis of recombinant ApoA-I 1-93 fragment. Similarly to the polypeptide isolated ex vivo, a pH switch from 7 to 4 induces a fast and reversible conformational transition to a helical state and leads to the identification of a key intermediate in the fibrillogenesis process. Limited proteolysis experiments suggested that the C-terminal region is involved in helix formation. The recombinant polypeptide generates fibrils at pH 4 on a time scale comparable with that of the native fragment. These findings open the way to studies on structural, thermodynamic, and kinetic aspects of ApoA-I fibrillogenesis.
- OSTI ID:
- 20857908
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 351; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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