Amyloid Fibrils Formed by the Programmed Cell Death Regulator Bcl-xL.

Alexandre Chenal; Charlotte Vendrely; Heidi Vitrac; Johanna C Karst; Alexis Gonneaud; Clément Blanchet; Sylvain Pichard; Elisabeth Garcia; Bénédicte Salin; Patrice Catty; Daniel Gillet; Nicolas Hussy; C. Marquette; Christine Almunia; Vincent Forge

doi:10.1016/j.jmb.2011.11.024

Journal articles

Amyloid Fibrils Formed by the Programmed Cell Death Regulator Bcl-xL.: Amyloid Fibrils from Bcl-xL

Alexandre Chenal ^{1, 2, *} Charlotte Vendrely ^{2, 3} Heidi Vitrac ² Johanna C Karst ¹ Alexis Gonneaud ² Clément Blanchet ² Sylvain Pichard ⁴ Elisabeth Garcia ² Bénédicte Salin ⁵ Patrice Catty ² Daniel Gillet ⁴ Nicolas Hussy ² C. Marquette ² Christine Almunia ⁶ Vincent Forge ^{2, *}

* Corresponding author

1 Biochimie des Interactions Macromoléculaires

2 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux

3 ERRMECe - Equipe de recherche sur les relations matrice extracellulaire-cellules

4 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)

5 IBGC - Institut de biochimie et génétique cellulaires

6 LEPC - Laboratoire d'Etude des Protéines Cibles

Abstract : The accumulation of amyloid fibers due to protein misfolding is associated with numerous human diseases. For example, the formation of amyloid deposits in neurodegenerative pathologies is correlated with abnormal apoptosis. We report here the in vitro formation of various types of aggregates by Bcl-xL, a protein of the Bcl-2 family involved in the regulation of apoptosis. Bcl-xL forms aggregates in three states, micelles, native-like fibrils, and amyloid fibers, and their biophysical characterization has been performed in detail. Bcl-xL remains in its native state within micelles and native-like fibrils, and our results suggest that native-like fibrils are formed by the association of micelles. Formation of amyloid structures, that is, nonnative intermolecular β-sheets, is favored by the proximity of proteins within fibrils at the expense of the Bcl-xL native structure. Finally, we provide evidence of a direct relationship between the amyloid character of the fibers and the tertiary-structure stability of the native Bcl-xL. The potential causality between the accumulation of Bcl-xL into amyloid deposits and abnormal apoptosis during neurodegenerative diseases is discussed.

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Journal articles

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Life Sciences [q-bio] / Biochemistry, Molecular Biology / Biophysics

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Amyloid Fibrils Formed by the Programmed Cell Death Regulator Bcl-xL.: Amyloid Fibrils from Bcl-xL

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Amyloid Fibrils Formed by the Programmed Cell Death Regulator Bcl-xL.: Amyloid Fibrils from Bcl-xL

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