Folding and fibrillogenesis

Clues from β2-microglobulin

Enrico Rennella, Alessandra Corazza, Sofia Giorgetti, Federico Fogolari, Paolo Viglino, Riccardo Porcari, Laura Verga, Monica Stoppini, Vittorio Bellotti, Gennaro Esposito

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Renal failure impairs the clearance of β2-microglobulin from the serum, with the result that this protein accumulates in joints under the form of amyloid fibrils. While the molecular mechanism leading to deposition of amyloid in vivo is not totally understood, some organic compounds, such as trifluoroethanol (TFE), are commonly used to promote the elongation of amyloid fibrils in vitro. This article gives some insights into the structural properties and the conformational states of β2-microglobulin in the presence of TFE, using both the wild-type protein and the mutant Trp60Gly. The structure of the native state of the protein is rather insensitive to the presence of the alcohol, but the stability of this state is lowered in comparison to some other conformational states. In particular, a native-like folding intermediate is observed in the presence of moderate concentrations of TFE. Instead, at higher concentrations of the alcohol, the population of a disordered native-unlike state is dominant and correlates with the ability to elongate fibrils.

Original languageEnglish
Pages (from-to)286-297
Number of pages12
JournalJournal of Molecular Biology
Volume401
Issue number2
DOIs
Publication statusPublished - Aug 2010

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Trifluoroethanol
Amyloid
Alcohols
Mutant Proteins
Renal Insufficiency
Proteins
Joints
Serum
Population

Keywords

  • β-microglobulin
  • Amyloid fibrils
  • Dialysis-related amyloidosis
  • Folding intermediate
  • Protein thermodynamics

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Rennella, E., Corazza, A., Giorgetti, S., Fogolari, F., Viglino, P., Porcari, R., ... Esposito, G. (2010). Folding and fibrillogenesis: Clues from β2-microglobulin. Journal of Molecular Biology, 401(2), 286-297. https://doi.org/10.1016/j.jmb.2010.06.016

Folding and fibrillogenesis : Clues from β2-microglobulin. / Rennella, Enrico; Corazza, Alessandra; Giorgetti, Sofia; Fogolari, Federico; Viglino, Paolo; Porcari, Riccardo; Verga, Laura; Stoppini, Monica; Bellotti, Vittorio; Esposito, Gennaro.

In: Journal of Molecular Biology, Vol. 401, No. 2, 08.2010, p. 286-297.

Research output: Contribution to journalArticle

Rennella, E, Corazza, A, Giorgetti, S, Fogolari, F, Viglino, P, Porcari, R, Verga, L, Stoppini, M, Bellotti, V & Esposito, G 2010, 'Folding and fibrillogenesis: Clues from β2-microglobulin', Journal of Molecular Biology, vol. 401, no. 2, pp. 286-297. https://doi.org/10.1016/j.jmb.2010.06.016
Rennella E, Corazza A, Giorgetti S, Fogolari F, Viglino P, Porcari R et al. Folding and fibrillogenesis: Clues from β2-microglobulin. Journal of Molecular Biology. 2010 Aug;401(2):286-297. https://doi.org/10.1016/j.jmb.2010.06.016
Rennella, Enrico ; Corazza, Alessandra ; Giorgetti, Sofia ; Fogolari, Federico ; Viglino, Paolo ; Porcari, Riccardo ; Verga, Laura ; Stoppini, Monica ; Bellotti, Vittorio ; Esposito, Gennaro. / Folding and fibrillogenesis : Clues from β2-microglobulin. In: Journal of Molecular Biology. 2010 ; Vol. 401, No. 2. pp. 286-297.
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