Evidence map›Paper›PMID 28150709›Full record

ArticleScientific reports2017

The conserved macrodomains of the non-structural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases.

Laura Eckei, Sarah Krieg, Mareike Bütepage, Anne Lehmann, Annika Gross, Barbara Lippok, Alexander R Grimm, Beate M Kümmerer, Giulia Rossetti, Bernhard Lüscher and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

103 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.

  1. Pooled it
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  19. Review
  20. Mutation of a highly conserved isoleucine residue in loop 2 of severalbioRxiv : the preprint server for biology · 2024
    Article

43 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

11 authors at 3 institutions in 1 country.

Laura EckeiInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Sarah KriegInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Mareike BütepageInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Anne LehmannInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Annika GrossInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Barbara LippokInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Alexander R GrimmInstitute of Biotechnology, RWTH Aachen University, 52074 Aachen, Germany.
Beate M KümmererInstitute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany.
Giulia RossettiComputational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425, Jülich, Germany.
Bernhard LüscherInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
Patricia VerheugdInstitute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52057 Aachen, Germany.
RWTH Aachen University · DEForschungszentrum Jülich · DEUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human pathogenic positive single strand RNA ((+)ssRNA) viruses, including Chikungunya virus, pose severe health problems as for many neither efficient vaccines nor therapeutic strategies exist. To interfere with propagation, viral enzymatic activities are considered potential targets. Here we addressed the function of the viral macrodomains, conserved folds of non-structural proteins of many (+)ssRNA viruses. Macrodomains are closely associated with ADP-ribose function and metabolism. ADP-ribosylation is a post-translational modification controlling various cellular processes, including DNA repair, transcription and stress response. We found that the viral macrodomains possess broad hydrolase activity towards mono-ADP-ribosylated substrates of the mono-ADP-ribosyltransferases ARTD7, ARTD8 and ARTD10 (aka PARP15, PARP14 and PARP10, respectively), reverting this post-translational modification both in vitro and in cells. In contrast, the viral macrodomains possess only weak activity towards poly-ADP-ribose chains synthesized by ARTD1 (aka PARP1). Unlike poly-ADP-ribosylglycohydrolase, which hydrolyzes poly-ADP-ribose chains to individual ADP-ribose units but cannot cleave the amino acid side chain - ADP-ribose bond, the different viral macrodomains release poly-ADP-ribose chains with distinct efficiency. Mutational and structural analyses identified key amino acids for hydrolase activity of the Chikungunya viral macrodomain. Moreover, ARTD8 and ARTD10 are induced by innate immune mechanisms, suggesting that the control of mono-ADP-ribosylation is part of a host-pathogen conflict.

Indexed as

CatalysisChikungunya virusConserved SequenceEnzyme ActivationHumansHydrolysisModels, MolecularMutationPoly Adenosine Diphosphate RibosePoly(ADP-ribose) PolymerasesProtein ConformationProtein Interaction Domains and MotifsProto-Oncogene ProteinsRNA VirusesSubstrate SpecificityViral Nonstructural ProteinsPARP10 protein, humanPoly Adenosine Diphosphate RibosePoly(ADP-ribose) PolymerasesProto-Oncogene ProteinsViral Nonstructural Proteins

Identifiers

PMID28150709
PMCPMC5288732
OpenAlexW2584528688

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.