Evidence mapPaperPMID 33112230Full record

ArticleeLife2020

Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state.

Kazi Rahman, Charles A Coomer, Saliha Majdoul, Selena Y Ding, Sergi Padilla-Parra, Alex A Compton

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 73 citations in OpenAlex.

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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 2 countries.

Kazi Rahman *HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, United States.ORCID 0000-0003-2986-0007
Charles A Coomer *HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, United States.ORCID 0000-0003-2523-6485
Saliha MajdoulHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, United States.ORCID 0000-0002-0530-6354
Selena Y DingHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, United States.ORCID 0000-0002-4413-644X
Sergi Padilla-ParraCellular Imaging Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-8010-9481
Alex A ComptonHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, United States.ORCID 0000-0002-7508-4953
National Cancer Institute · USCentre for Human Genetics · GB

Funding

European Research Council ERC-2019-CoG-863869 FUSION
6 · The paper itself

Abstract

The interferon-inducible transmembrane (IFITM) proteins belong to the Dispanin/CD225 family and inhibit diverse virus infections. IFITM3 reduces membrane fusion between cells and virions through a poorly characterized mechanism. Mutation of proline-rich transmembrane protein 2 (PRRT2), a regulator of neurotransmitter release, at glycine-305 was previously linked to paroxysmal neurological disorders in humans. Here, we show that glycine-305 and the homologous site in IFITM3, glycine-95, drive protein oligomerization from within a GxxxG motif. Mutation of glycine-95 (and to a lesser extent, glycine-91) disrupted IFITM3 oligomerization and reduced its antiviral activity against Influenza A virus. An oligomerization-defective variant was used to reveal that IFITM3 promotes membrane rigidity in a glycine-95-dependent and amphipathic helix-dependent manner. Furthermore, a compound which counteracts virus inhibition by IFITM3, Amphotericin B, prevented the IFITM3-mediated rigidification of membranes. Overall, these data suggest that IFITM3 oligomers inhibit virus-cell fusion by promoting membrane rigidity.

Indexed as

Amino Acid MotifsCell LineHEK293 CellsHumansInfluenza A virusInfluenza, HumanMembrane ProteinsRNA-Binding ProteinsVirus InternalizationIFITM3 protein, humanMembrane ProteinsRNA-Binding Proteinsevolutionary biologyfusionhumanIFITMimmunologyinflammationmembraneoligomerizationPRRT2virus

Identifiers

PMID33112230
PMCPMC7665892
OpenAlexW3094879454

What Socratic holds

Textmetadata
LicenceCC0
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 Socratic graph.