Evidence map›Paper›PMID 31199872›Full record

ArticleNucleic acids research2019

Dynamic ensemble of HIV-1 RRE stem IIB reveals non-native conformations that disrupt the Rev-binding site.

Chia-Chieh Chu, Raphael Plangger, Christoph Kreutz, Hashim M Al-Hashimi

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

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  16. A quantitative model predicts how mNature communications · 2021
    Article
  17. HIV-based lentiviral vectors: origin and sequence differences.Molecular therapy. Methods & clinical development · 2021
    Article
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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

4 authors at 2 institutions in 2 countries.

Chia-Chieh ChuDepartment of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Raphael PlanggerInstitute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Universität Innsbruck, 6020 Innsbruck, Austria.
Christoph KreutzInstitute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Universität Innsbruck, 6020 Innsbruck, Austria.
Hashim M Al-HashimiDepartment of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Duke University · USUniversität Innsbruck · AT

Funding

Austrian Science Fund FWF P 28725Austrian Science Fund FWF P 30370
6 · The paper itself

Abstract

The HIV-1 Rev response element (RRE) RNA element mediates the nuclear export of intron containing viral RNAs by forming an oligomeric complex with the viral protein Rev. Stem IIB and nearby stem II three-way junction nucleate oligomerization through cooperative binding of two Rev molecules. Conformational flexibility at this RRE region has been shown to be important for Rev binding. However, the nature of the flexibility has remained elusive. Here, using NMR relaxation dispersion, including a new strategy for directly observing transient conformational states in large RNAs, we find that stem IIB alone or when part of the larger RREII three-way junction robustly exists in dynamic equilibrium with non-native excited state (ES) conformations that have a combined population of ∼20%. The ESs disrupt the Rev-binding site by changing local secondary structure, and their stabilization via point substitution mutations decreases the binding affinity to the Rev arginine-rich motif (ARM) by 15- to 80-fold. The ensemble clarifies the conformational flexibility observed in stem IIB, reveals long-range conformational coupling between stem IIB and the three-way junction that may play roles in cooperative Rev binding, and also identifies non-native RRE conformational states as new targets for the development of anti-HIV therapeutics.

Indexed as

Genes, envAmino Acid SequenceBinding SitesHIV-1MagnesiumNuclear Magnetic Resonance, BiomolecularNucleic Acid Conformationrev Gene Products, Human Immunodeficiency VirusMagnesiumrev Gene Products, Human Immunodeficiency Virusrev protein, Human Immunodeficiency Virus-1

Identifiers

PMID31199872
PMCPMC6649712
OpenAlexW2950137298

What OpenQuestion holds

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LicenceCC BY
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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.