Evidence map›Paper›PMID 25644603›Full record

ArticleGenes & development2015

Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila.

Yuxuan Pang, Xiao-chen Bai, Chuangye Yan, Qi Hao, Zheqin Chen, Jia-Wei Wang, Sjors H W Scheres, Yigong Shi

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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

32 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Dark and Dronc activation inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Structural insights into CED-3 activation.Life science alliance · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. New insights into apoptosome structure and function.Cell death and differentiation · 2018
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

8 authors at 5 institutions in 3 countries.

Yuxuan PangMinistry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
Xiao-chen BaiMedical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Chuangye YanMinistry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
Qi HaoMinistry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
Zheqin ChenMinistry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
Jia-Wei WangCenter for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
Sjors H W ScheresMedical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom shi-lab@tsinghua.edu.cn scheres@mrc-lmb.cam.ac.uk.
Yigong ShiMinistry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; shi-lab@tsinghua.edu.cn scheres@mrc-lmb.cam.ac.uk.
Center for Life Sciences · CNKing Center · USTsinghua University · CNMedical Research Council · GBMRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_UP_A025_1013
6 · The paper itself

Abstract

Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome.

Indexed as

Models, MolecularAnimalsApoptosomesCaspasesDrosophilaDrosophila ProteinsEnzyme ActivationProtein BindingProtein Structure, TertiaryApoptosomesCaspasesDrosophila Proteinsapoptosiscaspase activationcryo-EM structureDarkDroncprogrammed cell death

Identifiers

PMID25644603
PMCPMC4318144
OpenAlexW2130611260

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.