Evidence map›Paper›PMID 25829498›Full record

ArticleThe Journal of biological chemistry2015

Role of nucleotide binding and GTPase domain dimerization in dynamin-like myxovirus resistance protein A for GTPase activation and antiviral activity.

Alexej Dick, Laura Graf, Daniel Olal, Alexander von der Malsburg, Song Gao, Georg Kochs, Oliver Daumke

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. 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
4.7field-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

42 citing papers in PubMed, 63 citations in OpenAlex.

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  18. HIV-1 resists MxB inhibition of viral Rev protein.Emerging microbes & infections · 2020
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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

7 authors at 4 institutions in 2 countries.

Alexej DickFrom the Max-Delbrück Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, the Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
Laura Grafthe Institute of Virology, University Medical Center, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany, the Spemann Graduate School of Biology and Medicine, University of Freiburg, Albertstrasse 19a, 79104 Freiburg, Germany, and.
Daniel OlalFrom the Max-Delbrück Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Alexander von der Malsburgthe Institute of Virology, University Medical Center, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
Song Gaothe Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Georg Kochsthe Institute of Virology, University Medical Center, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany, the Spemann Graduate School of Biology and Medicine, University of Freiburg, Albertstrasse 19a, 79104 Freiburg, Germany, and georg.kochs@uniklinik-freiburg.de.
Oliver DaumkeFrom the Max-Delbrück Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, the Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany, oliver.daumke@mdc-berlin.de.
University Medical Center Freiburg · DEMax Delbrück Center · DEFreie Universität Berlin · DESun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myxovirus resistance (Mx) GTPases are induced by interferon and inhibit multiple viruses, including influenza and human immunodeficiency viruses. They have the characteristic domain architecture of dynamin-related proteins with an N-terminal GTPase (G) domain, a bundle signaling element, and a C-terminal stalk responsible for self-assembly and effector functions. Human MxA (also called MX1) is expressed in the cytoplasm and is partly associated with membranes of the smooth endoplasmic reticulum. It shows a protein concentration-dependent increase in GTPase activity, indicating regulation of GTP hydrolysis via G domain dimerization. Here, we characterized a panel of G domain mutants in MxA to clarify the role of GTP binding and the importance of the G domain interface for the catalytic and antiviral function of MxA. Residues in the catalytic center of MxA and the nucleotide itself were essential for G domain dimerization and catalytic activation. In pulldown experiments, MxA recognized Thogoto virus nucleocapsid proteins independently of nucleotide binding. However, both nucleotide binding and hydrolysis were required for the antiviral activity against Thogoto, influenza, and La Crosse viruses. We further demonstrate that GTP binding facilitates formation of stable MxA assemblies associated with endoplasmic reticulum membranes, whereas nucleotide hydrolysis promotes dynamic redistribution of MxA from cellular membranes to viral targets. Our study highlights the role of nucleotide binding and hydrolysis for the intracellular dynamics of MxA during its antiviral action.

Indexed as

Cell LineEndoplasmic ReticulumEnzyme ActivationGTP PhosphohydrolasesHumansHydrolysisIntracellular MembranesLa Crosse virusMyxovirus Resistance ProteinsNucleocapsid ProteinsOrthomyxoviridaeProtein MultimerizationProtein Structure, TertiaryThogotovirusGTP PhosphohydrolasesMX1 protein, humanMyxovirus Resistance ProteinsNucleocapsid Proteinsantiviral responsecatalytic mechanismdynamin-like proteinG proteininnate immunityinterferonmembraneMx proteinsviral replication

Identifiers

PMID25829498
PMCPMC4432294
OpenAlexW2026219049

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.