Evidence map›Paper›PMID 9405358›Full record

ArticleThe EMBO journal1997

Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.

R Uellner, M J Zvelebil, J Hopkins, J Jones, L K MacDougall, B P Morgan, E Podack, M D Waterfield, G M Griffiths

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

57 citing papers in PubMed, 197 citations in OpenAlex.

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  16. Cystatin F as a regulator of immune cell cytotoxicity.Cancer immunology, immunotherapy : CII · 2018
    Review
  17. Article
  18. Article
  19. Antigen-specific CD8Nature communications · 2017
    Article
  20. [Expression of porforin and granzyme B in familial hemophagocytic lymphohistiocytosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016
    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

9 authors at 1 institution in 1 country.

R UellnerMRC Laboratory of Molecular Biology, University College London, Gower St, London WC1E 6BT, UK.
M J Zvelebil
J Hopkins
J Jones
L K MacDougall
B P Morgan
E Podack
M D Waterfield
G M Griffiths
University College London · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Perforin is a secreted protein synthesized by activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It is a key component of the lytic machinery of these cells, being able to insert into the plasma membrane of targeted cells, forming a pore which leads to their destruction. Here we analyse the synthesis, processing and intracellular transport of perforin in the NK cell line YT. Perforin is synthesized as a 70 kDa inactive precursor which is cleaved at the C-terminus to yield a 60 kDa active form. This proteolytic cleavage occurs in an acidic compartment and can be inhibited by incubation of the cells in ammonium chloride, concanamycin A, leupeptin and E-64. The increased lytic activity of the cleaved form can be demonstrated by killing assays in which cleavage of the pro-piece is inhibited. Epitope mapping reveals that cleavage of the pro-piece occurs at the boundary of a C2 domain, which we show is able to bind phospholipid membranes in a calcium-dependent manner. We propose that removal of the pro-piece, which contains a bulky glycan, allows the C2 domain to interact with phospholipid membranes and initiate perforin pore formation.

Indexed as

Protein ConformationProtein Processing, Post-TranslationalAmino Acid SequenceAnimalsBinding SitesCell LineCytotoxicity, ImmunologicGlycosylationHexosaminidasesHumansIsoenzymesKiller Cells, NaturalLiposomesLymphocyte ActivationMembrane GlycoproteinsModels, MolecularHexosaminidasesIsoenzymesLiposomesMembrane GlycoproteinsPerforinPhospholipase C deltaPhospholipidsPore Forming Cytotoxic ProteinsRecombinant ProteinsType C Phospholipases

Identifiers

PMID9405358
PMCPMC1170329
OpenAlexW1981531114

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.