Evidence map›Paper›PMID 27217060›Full record

ArticleNature communications2016

Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies.

Sweta Iyer, Khatira Anwari, Amber E Alsop, Wai Shan Yuen, David C S Huang, John Carroll, Nicholas A Smith, Brian J Smith, Grant Dewson, Ruth M Kluck

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.Nature reviews. Molecular cell biology · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Physiological and pharmacological modulation of BAX.Trends in pharmacological sciences · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins.Cold Spring Harbor perspectives in biology · 2020
    Review
  17. Small-molecule allosteric inhibitors of BAX.Nature chemical biology · 2019
    Article
  18. Article
  19. Article
  20. Neuronal Cell Death.Physiological reviews · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Sweta IyerMolecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.
Khatira AnwariMolecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.
Amber E AlsopMolecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.
Wai Shan YuenDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
David C S HuangCancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.
John CarrollDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
Nicholas A SmithDepartment of Chemistry and Physics, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria 3086, Australia.
Brian J SmithDepartment of Chemistry and Physics, La Trobe Institute for Molecular Sciences, La Trobe University, Victoria 3086, Australia.
Grant DewsonCell Signalling and Cell Death Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.
Ruth M KluckMolecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia.ORCID 0000-0002-7101-1925
Walter and Eliza Hall Institute of Medical Research · AULa Trobe University · AUMonash University · AU

Funding

Medical Research Council G1001705
6 · The paper itself

Abstract

During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the α2-α5 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the α1-α2 loop. A monoclonal antibody (clone 7D10) binds close to α1 in non-activated Bak to induce conformational change, oligomerization, and cytochrome c release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to α1. An antibody (clone 3C10) to the Bax α1-α2 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates α1; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under α1. Our identification of the α1-α2 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins.

Indexed as

AnimalsAntibodies, MonoclonalApoptosisbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCells, CulturedCytochromes cCytosolEpitope MappingEpitopesFemaleFibroblastsGene Knockout TechniquesHumansMiceMice, Inbred C57BLAntibodies, MonoclonalBAK1 protein, humanBak1 protein, mouseBAX protein, humanBax protein, mousebcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCytochromes cEpitopes

Identifiers

PMID27217060
PMCPMC4890306
OpenAlexW2405490536

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.