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Scientific article
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Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association

Published inStructure, vol. 29, no. 2, p. 114-124.e3
Publication date2021-02
Abstract

Bcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome.

eng
Keywords
  • BH3
  • Bcl-xL
  • Bim peptides
  • DEER
  • EPR
  • X-ray
  • Apoptosis
Affiliation Not a UNIGE publication
Citation (ISO format)
ASSAFA, Tufa E. et al. Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association. In: Structure, 2021, vol. 29, n° 2, p. 114–124.e3. doi: 10.1016/j.str.2020.09.002
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ISSN of the journal0969-2126
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