The importance of evolutionarily conserved C-terminal basic residues for the stability of proapoptotic Bax protein

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Abstract

Bax is a protein that promotes apoptosis (a form of cell death). The atomistic details of the mechanism by which Bax is activated during apoptosis remain a subject of debate. C-terminal basic residues in the sequence of Bax show remarkable conservation across a variety of species. The role of these charged residues in the stability of Bax was investigated by submitting substituted mutants to molecular dynamics simulations at high temperatures. Mutation of either or both K189 and K190 led to dramatic changes in helical content, radius of gyration, proximity of the C terminus to the core of the protein, exposure of the BH3 domain, and bundling of the core. These results suggest a critical role of positively charged residues close to the C terminus in the structural stability of Bax.

Original languageEnglish
Pages (from-to)976-986
Number of pages11
JournalFEBS Open Bio
Volume6
Issue number10
DOIs
StatePublished - 1 Oct 2016

Keywords

  • apoptosis
  • molecular dynamics
  • protein stability

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