The pro-apoptotic domain of BIM protein forms toxic amyloid fibrils

Ravit Malishev, Shani Ben-Zichri, Ofek Oren, Nitzan Shauloff, Tal Peretz, Ran Taube, Niv Papo, Raz Jelinek

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BIM is a key apoptotic protein, participating in diverse cellular processes. Interestingly, recent studies have hypothesized that BIM is associated with the extensive neuronal cell death encountered in protein misfolding diseases, such as Alzheimer’s disease. Here, we report that the core pro-apoptotic domain of BIM, the BIM-BH3 motif, forms ubiquitous amyloid fibrils. The BIM-BH3 fibrils exhibit cytotoxicity, disrupt mitochondrial functions, and modulate the structures and dynamics of mitochondrial membrane mimics. Interestingly, a slightly longer peptide in which BIM-BH3 was flanked by four additional residues, widely employed as a model of the pro-apoptotic core domain of BIM, did not form fibrils, nor exhibited cell disruptive properties. The experimental data suggest a new mechanistic role for the BIM-BH3 domain, and demonstrate, for the first time, that an apoptotic peptide forms toxic amyloid fibrils.

Original languageEnglish
Pages (from-to)2145-2155
Number of pages11
JournalCellular and Molecular Life Sciences
Volume78
Issue number5
DOIs
StatePublished - 1 Mar 2021

Keywords

  • Apoptosis
  • BIM
  • Bcl-2 proteins
  • Beta-amyloid
  • Fibrils
  • Mitochondria

Fingerprint

Dive into the research topics of 'The pro-apoptotic domain of BIM protein forms toxic amyloid fibrils'. Together they form a unique fingerprint.

Cite this