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Updated: Nov 10, 2025

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Structure of detergent-activated BAK dimers derived from the inert monomer

Richard W Birkinshaw1, Sweta Iyer1, Daisy Lio1

  • 1The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Molecular Cell
|April 1, 2021
PubMed

Insights

Researchers discovered the smallest functional unit of BAK and BAX proteins, revealing their core dimers in a membrane-disrupting conformation. This finding clarifies how these apoptotic effectors activate to destroy mitochondrial integrity.

Area of Science:

  • Molecular biology
  • Cell biology
  • Biochemistry

Background:

  • BAK (Bcl-2-associated X protein) and BAX (Bcl-2-associated X protein) are essential apoptotic effector molecules.
  • Existing data suggest core dimers (α2-α5) of BAK and BAX in their membrane-perturbing conformation.
  • Previous structural studies were limited to truncated constructs of the core domain.

Purpose of the Study:

  • To determine the crystal structure of activated BAK dimers, including the latch domain.
  • To provide direct evidence for the conformational change from inert BAK monomer to functional dimer.
  • To identify the smallest functional unit of BAK and BAX.

Main Methods:

  • Activation of monomeric BAK using the detergent C12E8.
  • Obtaining a crystal structure of BAK α2-α8 dimers (excluding N-terminal helix and C-terminal segment).
  • Analysis of dimer interfaces and conformational changes.

Main Results:

  • A crystal structure of activated BAK dimers (α2-α8) was obtained.
  • Core dimers were observed, linked by latch (α6-α8) domain contacts.
  • The structure revealed the extended latch domain in activated BAK dimers.
  • Direct evidence for the conformational change from monomer to functional dimer was provided.

Conclusions:

  • The identified dimer represents the smallest functional unit for recombinant BAK or BAX.
  • This structural insight clarifies the mechanism by which BAK and BAX induce mitochondrial outer membrane permeabilization.
  • The findings advance our understanding of apoptosis regulation at the molecular level.
Keywords:
ApoptosisBAKBAK activationBCL-2 family proteinsBH3-in-groove core dimersDetergent mediated dimerizationX-ray crystallographycytochrome c releasemembrane rupture

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