AI Article Synopsis

  • - The study focuses on the Bcl-2 family proteins in metazoans, which play key roles in regulating apoptosis, particularly in the early evolutionary stages of these organisms, specifically analyzing four trBcl-2 homologs in a primitive metazoan.
  • - Among these homologs, trBcl-2L1 and trBcl-2L2 are found to be antiapoptotic, while trBcl-2L3 and trBcl-2L4 are proapoptotic, with trBax and trBak having specific roles in permeabilizing mitochondrial membranes and regulating antiapoptotic activities.
  • - The findings also reveal that the structure of trBcl-2L2

Article Abstract

In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization of the four members of the Bcl-2 family in the most primitive metazoan, All four trBcl-2 homologs are multimotif Bcl-2 group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic Bcl-2 members, whereas trBcl-2L3 and trBcl-2L4 are homologs of proapoptotic Bax and Bak, respectively. trBax expression permeabilizes the mitochondrial outer membrane, while trBak operates as a BH3-only sensitizer repressing antiapoptotic activities of trBcl-2L1 and trBcl-2L2. The crystal structure of a trBcl-2L2:trBak BH3 complex reveals that trBcl-2L2 uses the canonical Bcl-2 ligand binding groove to sequester trBak BH3, indicating that the structural basis for apoptosis control is conserved from to mammals. Finally, we demonstrate that both trBax and trBak BH3 peptides bind selectively to human Bcl-2 homologs to sensitize cancer cells to chemotherapy treatment.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527217PMC
http://dx.doi.org/10.1126/sciadv.abc4149DOI Listing

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