title: Amyloid fibrils formed by the programmed cell death regulator Bcl-xL.
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.
authors: CEA, DSV, iRTSV, Laboratoire de Chimie et Biologie des Métaux (UMR 5249), CEA Grenoble, 17 Rue des Martyrs, Grenoble, F-38054, France.
authors: Alexandre
authors: A
authors: Chenal
authors: Charlotte
authors: C
authors: Vendrely
authors: Heidi
authors: H
authors: Vitrac
authors: Johanna C
authors: JC
authors: Karst
authors: Alexis
authors: A
authors: Gonneaud
authors: Clément E
authors: CE
authors: Blanchet
authors: Sylvain
authors: S
authors: Pichard
authors: Elisabeth
authors: E
authors: Garcia
authors: Bénédicte
authors: B
authors: Salin
authors: Patrice
authors: P
authors: Catty
authors: Daniel
authors: D
authors: Gillet
authors: Nicolas
authors: N
authors: Hussy
authors: Christel
authors: C
authors: Marquette
authors: Christine
authors: C
authors: Almunia
authors: Vincent
authors: V
authors: Forge
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D055503:Protein Multimerization; D055550:Protein Stability; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000682:Amyloid; C494811:BCL2L1 protein, human; D051020:bcl-X Protein