Cited by 573Cell death mechanisms and regulationEnzyme Structure and FunctionCancer-related Molecular Pathways

Bax Crystal Structures Reveal How BH3 Domains Activate Bax and Nucleate Its Oligomerization to Induce Apoptosis

Open access
Czabotar, Peter E., Westphal, Dana, Dewson, Grant, Ma, Stephen, Hockings, Colin, Fairlie, W. Douglas, Lee, Erinna F., Yao, Shenggen +6 more·2013·Cell

Abstract

In stressed cells, apoptosis ensues when Bcl-2 family members Bax or Bak oligomerize and permeabilize the mitochondrial outer membrane. Certain BH3-only relatives can directly activate them to mediate this pivotal, poorly understood step. To clarify the conformational changes that induce Bax oligomerization, we determined crystal structures of BaxΔC21 treated with detergents and BH3 peptides. The peptides bound the Bax canonical surface groove but, unlike their complexes with prosurvival relatives, dissociated Bax into two domains. The structures define the sequence signature of activator BH3 domains and reveal how they can activate Bax via its groove by favoring release of its BH3 domain. Furthermore, Bax helices α2-α5 alone adopted a symmetric homodimer structure, supporting the proposal that two Bax molecules insert their BH3 domain into each other's surface groove to nucleate oligomerization. A planar lipophilic surface on this homodimer may engage the membrane. Our results thus define critical Bax transitions toward apoptosis.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2012.12.031

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Activated BAX and BAK form homodimers (also heterodimers in specific settings), resulting in the release of BH3-only proteins and further dimer-by-dimer oligomerization.

    “The current view is that activated BAX and BAK form homodimers (also heterodimers in specific settings), resulting in the release of BH3-only proteins and further dimer-by-dimer oligomerization [76–83].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Czabotar, P. E., Westphal, D., Dewson, G., Ma, S., Hockings, C., Fairlie, W. D., Lee, E. F., Yao, S., Robin, A. Y., Smith, B. J., Huang, D. C. S., Kluck, R. M., Adams, J. M., & Colman, P. M.
Affiliations
  • The University of Melbourne (AU)
  • La Trobe University (AU)
Corresponding author
  • Czabotar, Peter E.
  • Colman, Peter M.
Venue
Cell
Publisher
Elsevier BV
Published
2013-01
Volume
152
Issue
3
Pages
519-531
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2142713529
Cited by
573
References
70
Citations by year
2026: 29 · 2025: 27 · 2024: 27 · 2023: 37 · 2022: 34 · 2021: 48 · 2020: 42 · 2019: 38 · 2018: 50 · 2017: 53 · 2016: 55 · 2015: 54 · 2014: 44 · 2013: 35
FWCI
28.05
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Leukemia and Lymphoma Society
  • Australian Government
  • Australian Cancer Research Foundation
  • Australian Synchrotron
  • Deutsche Forschungsgemeinschaft
  • State Government of Victoria
  • National Health and Medical Research Council
  • Cancer Council Victoria
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
Bax, BH3 domain, apoptosis, Bax oligomerization, Bcl-2 family proteins, mitochondrial outer membrane permeabilization, homodimer, surface grooves, conformational change, detergents
MeSH terms
Amino Acid Sequence, Animals, Embryo, Mammalian, Liposomes, Liver, Mitochondria, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Alignment, Apoptosis, Protein Structure, Tertiary, Crystallography, X-Ray, Dimerization, Cytochromes c, bcl-2-Associated X Protein, Mice, Hydrophobic and Hydrophilic Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review