Evidence map›Paper›PMID 21036904›Full record

ArticleThe Journal of biological chemistry2010

Heterodimerization of BAK and MCL-1 activated by detergent micelles.

Qian Liu, Kalle Gehring

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Many players in BCL-2 family affairs.Trends in biochemical sciences · 2014
    Review
  11. Review
  12. 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

2 authors at 1 institution in 1 country.

Qian LiuDepartment of Biochemistry, McGill University, Montreal, Quebec H3G 0B1, Canada.
Kalle Gehring
McGill University · CA

Funding

Canadian Institutes of Health Research MOP-81277
6 · The paper itself

Abstract

BAK is a key protein mediating mitochondrial outer membrane permeabilization; however, its behavior in the membrane is poorly understood. Here, we characterize the conformational changes in BAK and MCL-1 using detergents to mimic the membrane environment and study their interaction by in vitro pulldown experiments, size exclusion chromatography, titration calorimetry, and NMR spectroscopy. The nonionic detergent IGEPAL has little impact on the structure of MCL-1 but induces a conformational change in BAK, whereby its BH3 region is able to engage the hydrophobic groove of MCL-1. Although the zwitterionic detergent CHAPS induces only minor conformational changes in both proteins, it is still able to initiate heterodimerization. The complex of MCL-1 and BAK can be disrupted by a BID-BH3 peptide, which acts through binding to MCL-1, but a mutant peptide, BAK-BH3-L78A, with low affinity for MCL-1 failed to dissociate the complex. The mutation L78A in BAK prevented binding to MCL-1, thus demonstrating the essential role of the BH3 region of BAK in its regulation by MCL-1. Our results validate the current models for the activation of BAK and highlight the potential value of small molecule inhibitors that target MCL-1 directly.

Indexed as

MicellesModels, ChemicalProtein Multimerizationbcl-2 Homologous Antagonist-Killer ProteinBH3 Interacting Domain Death Agonist ProteinCholic AcidsDetergentsHumansMutationMyeloid Cell Leukemia Sequence 1 ProteinNuclear Magnetic Resonance, BiomolecularPeptidesProto-Oncogene Proteins c-bcl-23-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonateBAK1 protein, humanbcl-2 Homologous Antagonist-Killer ProteinBH3 Interacting Domain Death Agonist ProteinBID protein, humanCholic AcidsDetergentsMicellesMyeloid Cell Leukemia Sequence 1 ProteinPeptidesProto-Oncogene Proteins c-bcl-2

Identifiers

PMID21036904
PMCPMC3003418
OpenAlexW2062405425

What OpenQuestion holds

Textmetadata
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.