Evidence map›Paper›PMID 26869228›Full record

ArticleJournal of cell science2016

Mechanistic insights into the inhibition of Sec61-dependent co- and post-translational translocation by mycolactone.

Michael McKenna, Rachel E Simmonds, Stephen High

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
14.1field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 113 citations in OpenAlex.

  1. Trial
  2. Buruli ulcer.Nature reviews. Disease primers · 2025
    Review
  3. Article
  4. TheeLife · 2025
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Mechanism of Protein Translocation by the Sec61 Translocon Complex.Cold Spring Harbor perspectives in biology · 2023
    Review
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 1 country.

Michael McKennaFaculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.
Rachel E SimmondsDepartment of Microbial Sciences, School of Bioscience and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK.
Stephen HighFaculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester M13 9PT, UK stephen.high@manchester.ac.uk.
University of Manchester · GBUniversity of Surrey · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J014478/1Wellcome TrustWellcome Trust WT092744
6 · The paper itself

Abstract

The virulence factor mycolactone is responsible for the immunosuppression and tissue necrosis that characterise Buruli ulcer, a disease caused by infection with Mycobacterium ulcerans In this study, we confirm that Sec61, the protein-conducting channel that coordinates entry of secretory proteins into the endoplasmic reticulum, is a primary target of mycolactone, and characterise the nature of its inhibitory effect. We conclude that mycolactone constrains the ribosome-nascent-chain-Sec61 complex, consistent with its broad-ranging perturbation of the co-translational translocation of classical secretory proteins. In contrast, the effect of mycolactone on the post-translational ribosome-independent translocation of short secretory proteins through the Sec61 complex is dependent on both signal sequence hydrophobicity and the translocation competence of the mature domain. Changes to protease sensitivity strongly suggest that mycolactone acts by inducing a conformational change in the pore-forming Sec61α subunit. These findings establish that mycolactone inhibits Sec61-mediated protein translocation and highlight differences between the co- and post-translational routes that the Sec61 complex mediates. We propose that mycolactone also provides a useful tool for further delineating the molecular mechanisms of Sec61-dependent protein translocation.

Indexed as

AnimalsBuruli UlcerEndoplasmic ReticulumHumansMacrolidesMycobacterium ulceransProtein TransportRibosomesSEC Translocation ChannelsMacrolidesmycolactoneSEC Translocation ChannelsBuruli ulcerEndoplasmic reticulumMycobacterium ulceransMycolactoneSec61Short secretory protein

Identifiers

PMID26869228
PMCPMC4852723
OpenAlexW2252562117

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.