Evidence map›Paper›PMID 33205864›Full record

ArticleAngewandte Chemie (International ed. in English)2021

Dimer Organization of Membrane-Associated NS5A of Hepatitis C Virus as Determined by Highly Sensitive

Vlastimil Jirasko, Alons Lends, Nils-Alexander Lakomek, Marie-Laure Fogeron, Marco E Weber, Alexander A Malär, Susanne Penzel, Ralf Bartenschlager, Beat H Meier, Anja Böckmann

Open access · hybridAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

17 citing papers in PubMed, 49 citations in OpenAlex.

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  6. Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  8. Article
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  11. Optimisation ofPhysical chemistry chemical physics : PCCP · 2022
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  13. Chemical reviews · 2022
    Review
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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

10 authors at 3 institutions in 3 countries.

Vlastimil JiraskoPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0003-1561-1499
Alons LendsPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0001-7883-613X
Nils-Alexander LakomekPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0002-4285-6339
Marie-Laure FogeronMolecular Microbiology and Structural Biochemistry, Labex Ecofect, UMR 5086 CNRS, Université de Lyon 1, 7 passage du Vercors, 69367, Lyon, France.ORCID 0000-0002-2146-8740
Marco E WeberPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0001-9764-4862
Alexander A MalärPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0003-1026-9583
Susanne PenzelPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120, Heidelberg, Germany.ORCID 0000-0001-5601-9307
Beat H MeierPhysical Chemistry, ETH Zurich, 8093, Zurich, Switzerland.ORCID 0000-0002-9107-4464
Anja BöckmannMolecular Microbiology and Structural Biochemistry, Labex Ecofect, UMR 5086 CNRS, Université de Lyon 1, 7 passage du Vercors, 69367, Lyon, France.ORCID 0000-0001-8149-7941
ETH Zurich · CHUniversité Claude Bernard Lyon 1 · FRHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Hepatitis C virus nonstructural protein 5A (NS5A) is a membrane-associated protein involved in multiple steps of the viral life cycle. Direct-acting antivirals (DAAs) targeting NS5A are a cornerstone of antiviral therapy, but the mode-of-action of these drugs is poorly understood. This is due to the lack of information on the membrane-bound NS5A structure. Herein, we present the structural model of an NS5A AH-linker-D1 protein reconstituted as proteoliposomes. We use highly sensitive proton-detected solid-state NMR methods suitable to study samples generated through synthetic biology approaches. Spectra analyses disclose that both the AH membrane anchor and the linker are highly flexible. Paramagnetic relaxation enhancements (PRE) reveal that the dimer organization in lipids requires a new type of NS5A self-interaction not reflected in previous crystal structures. In conclusion, we provide the first characterization of NS5A AH-linker-D1 in a lipidic environment shedding light onto the mode-of-action of clinically used NS5A inhibitors.

Indexed as

HepacivirusLipid BilayersNuclear Magnetic Resonance, BiomolecularPhosphatidylethanolaminesProtein Conformation, alpha-HelicalProtein DomainsProtein MultimerizationProton Magnetic Resonance SpectroscopyRNA-Dependent RNA PolymeraseViral Nonstructural Proteins1,2-dipalmitoyl-3-phosphatidylethanolamineLipid BilayersNS-5 protein, hepatitis C virusPhosphatidylethanolaminesRNA-Dependent RNA PolymeraseViral Nonstructural Proteinscell-free synthesishepatitis C virusNS5Aparamagnetic relaxation enhancementsolid-state NMR

Identifiers

PMID33205864
PMCPMC7986703
OpenAlexW3098058476

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.