Evidence map›Paper›PMID 32064340›Full record

ArticleScience advances2020

Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity.

Tao Ni, Fang Jiao, Xiulian Yu, Saša Aden, Lucy Ginger, Sophie I Williams, Fangfang Bai, Vojtěch Pražák, Dimple Karia, Phillip Stansfeld and 5 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
9.9field-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

42 citing papers in PubMed, 74 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. For Better or Worse: The Impact of Necrotic Cell Death Modalities.Advances in experimental medicine and biology · 2025
    Review
  14. Acid-resistant enzymes: the acquisition strategies and applications.Applied microbiology and biotechnology · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. The evolutionary diversification and antimicrobial potential of MPEG1 in Metazoa.Computational and structural biotechnology journal · 2023
    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

15 authors at 5 institutions in 3 countries.

Tao NiDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0001-7268-0306
Fang JiaoDepartment of Anesthesiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, USA.ORCID 0000-0001-5087-6228
Xiulian YuDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0002-8853-1775
Saša AdenDepartment of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.ORCID 0000-0002-0045-223X
Lucy GingerDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Sophie I WilliamsDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0003-2638-6004
Fangfang BaiDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Vojtěch PražákDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0001-8149-218X
Dimple KariaDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0002-3776-1650
Phillip StansfeldDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.ORCID 0000-0001-8800-7669
Peijun ZhangDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0003-1803-691X
George MunsonDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.ORCID 0000-0002-3692-8199
Gregor AnderluhDepartment of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.ORCID 0000-0002-9916-8465
Simon ScheuringDepartment of Anesthesiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, USA.ORCID 0000-0003-3534-069X
Robert J C GilbertDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.ORCID 0000-0001-9336-5604
Centre for Human Genetics · GBCornell University · USNational Institute of Chemistry · SIUniversity of Miami · USUniversity of Oxford · GB

Funding

Killing of intracellular bacteria by Perforin-2R01AI110810 · NIAID · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MUNSON, GEORGE PATRICK · 2015 to 2019
$2.1M
Biotechnology and Biological Sciences Research Council BB/I019855/1Biotechnology and Biological Sciences Research Council BB/M011224/1Medical Research Council MR/N000331/1NIAID NIH HHS R01 AI110810Wellcome Trust 206422/Z/17/Z
6 · The paper itself

Abstract

Perforin-2 (MPEG1) is thought to enable the killing of invading microbes engulfed by macrophages and other phagocytes, forming pores in their membranes. Loss of perforin-2 renders individual phagocytes and whole organisms significantly more susceptible to bacterial pathogens. Here, we reveal the mechanism of perforin-2 activation and activity using atomic structures of pre-pore and pore assemblies, high-speed atomic force microscopy, and functional assays. Perforin-2 forms a pre-pore assembly in which its pore-forming domain points in the opposite direction to its membrane-targeting domain. Acidification then triggers pore formation, via a 180° conformational change. This novel and unexpected mechanism prevents premature bactericidal attack and may have played a key role in the evolution of all perforin family proteins.

Indexed as

Evolution, MolecularProtein ConformationAnimalsBacteriaHumansImmunity, InnateMacrophagesMammalsMicePhagocytesProfilinsPfn2 protein, mouseProfilins

Identifiers

PMID32064340
PMCPMC6989145
OpenAlexW2989578970

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.