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An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane.

Fujiao LvFei QiZhi ZhangMaorong WenJustin KaleAlessandro PiaiLingyu DuShuqing WangLiujuan ZhouYaqing YangBin WuZhijun LiuJuan Del RosarioJustin PogmoreJames J ChouDavid William AndrewsJialing LinBo Ouyang
Published in: The EMBO journal (2021)
Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high-resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both types of protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.
Keyphrases
  • fatty acid
  • induced apoptosis
  • high resolution
  • oxidative stress
  • cell death
  • magnetic resonance
  • signaling pathway
  • left ventricular
  • small molecule
  • reactive oxygen species
  • cell proliferation
  • tandem mass spectrometry