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Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation

Chenyi Liao1, Zhi Zhang2, Justin Kale3,4

  • 1Department of Chemistry, University of Vermont, Burlington, VT 05405, USA.

Scientific Reports
|July 7, 2016
PubMed

Insights

Bax protein's helix α9 dimerizes in the mitochondrial outer membrane, forming pores. Distinct dimer conformations and lipid interactions drive this process, crucial for apoptosis regulation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Bax protein's helix α9 dimerizes at the mitochondrial outer membrane (MOM), contributing to apoptotic pore formation.
  • The precise molecular mechanisms by which different dimer conformations influence pore formation remain poorly understood.

Purpose of the Study:

  • To investigate the conformational states of the Bax helix α9 dimer within a MOM model.
  • To elucidate the role of dimer conformation and lipid interactions in Bax-mediated apoptosis.

Main Methods:

  • Computational simulations of Bax α9 dimer in a MOM model.
  • Site-specific mutagenesis and crosslinking of α9 helices.
  • Experimental validation of computational findings.

Main Results:

  • Confirmed the importance of the membrane environment for α9 stability and dimerization.
  • Revealed distinct lipid-binding preferences for different dimer conformations.
  • Discovered and experimentally validated a crucial iso-parallel dimer mediating conformational transitions.

Conclusions:

  • Bax helix α9 stability and dimerization are critical within the MOM.
  • Dimer heterogeneity and specific MOM lipid interactions facilitate Bax activation and proteolipidic pore formation.
  • This study provides molecular insights into apoptosis regulation by Bax.

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