Evidence map›Paper›PMID 33199689›Full record

ArticleNature communications2020

Structural basis for tuning activity and membrane specificity of bacterial cytolysins.

Nita R Shah, Tomas B Voisin, Edward S Parsons, Courtney M Boyd, Bart W Hoogenboom, Doryen Bubeck

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. First crystal structure of the DUF2436 domain of virulence proteins from Porphyromonas gingivalis.Acta crystallographica. Section F, Structural biology communications · 2024
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Bacterial pore-forming toxins.Microbiology (Reading, England) · 2022
    Article
  15. Article
  16. Challenges and approaches to studying pore-forming proteins.Biochemical Society transactions · 2021
    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

6 authors at 2 institutions in 1 country.

Nita R ShahDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Tomas B VoisinDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Edward S ParsonsLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
Courtney M BoydDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK.
Bart W HoogenboomLondon Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.ORCID 0000-0002-8882-4324
Doryen BubeckDepartment of Life Sciences, Sir Ernst Chain Building, Imperial College London, London, SW7 2AZ, UK. d.bubeck@imperial.ac.uk.ORCID 0000-0001-8241-9697
Imperial College London · GBLondon Centre for Nanotechnology · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J014575/1Biotechnology and Biological Sciences Research Council BB/M011178/1Cancer Research UK 16099Cancer Research UK C26409/A16099Medical Research Council MR/R000328/1Wellcome Trust
6 · The paper itself

Abstract

Cholesterol-dependent cytolysins (CDCs) are pore-forming proteins that serve as major virulence factors for pathogenic bacteria. They target eukaryotic cells using different mechanisms, but all require the presence of cholesterol to pierce lipid bilayers. How CDCs use cholesterol to selectively lyse cells is essential for understanding virulence strategies of several pathogenic bacteria, and for repurposing CDCs to kill new cellular targets. Here we address that question by trapping an early state of pore formation for the CDC intermedilysin, bound to the human immune receptor CD59 in a nanodisc model membrane. Our cryo electron microscopy map reveals structural transitions required for oligomerization, which include the lateral movement of a key amphipathic helix. We demonstrate that the charge of this helix is crucial for tuning lytic activity of CDCs. Furthermore, we discover modifications that overcome the requirement of cholesterol for membrane rupture, which may facilitate engineering the target-cell specificity of pore-forming proteins.

Indexed as

CD59 AntigensCell MembraneCryoelectron MicroscopyCytotoxinsHumansModels, BiologicalModels, MolecularMutationProtein Structure, SecondaryStructure-Activity RelationshipCD59 AntigensCD59 protein, humanCytotoxins

Identifiers

PMID33199689
PMCPMC7669874
OpenAlexW3098376997

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.