The Pro-apoptotic Domain of BIM Protein Forms Toxic Amyloid Fibrils

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2020 Aug 27

PMID 32844279

Citations 4

Authors

Ravit Malishev

Shani Ben-Zichri

Ofek Oren

Nitzan Shauloff

Tal Peretz

Ran Taube

Niv Papo

Raz Jelinek

Affiliations

Soon will be listed here.

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.

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