Evidence map›Paper›PMID 29122886›Full record

ArticleThe Journal of biological chemistry2018

Mechanism of polypurine tract primer generation by HIV-1 reverse transcriptase.

Małgorzata Figiel, Miroslav Krepl, Sangwoo Park, Jarosław Poznański, Krzysztof Skowronek, Agnieszka Gołąb, Taekjip Ha, Jiří Šponer, Marcin Nowotny

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

15 citing papers in PubMed, 26 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

9 authors at 5 institutions in 3 countries.

Małgorzata FigielLaboratory of Protein Structure, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Miroslav KreplInstitute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic; Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University Olomouc, 771 46 Olomouc, Czech Republic.
Sangwoo ParkDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, Maryland 21205.
Jarosław PoznańskiInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Krzysztof SkowronekBiophysics Core Facility, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Agnieszka GołąbLaboratory of Protein Structure, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Taekjip HaDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University, Baltimore, Maryland 21205; Howard Hughes Medical Institute, Baltimore, Maryland 21205; Department of Biophysics, The Johns Hopkins University, Baltimore, Maryland 21205; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland 21205.
Jiří ŠponerBiophysics Core Facility, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland; Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University Olomouc, 771 46 Olomouc, Czech Republic.
Marcin NowotnyLaboratory of Protein Structure, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. Electronic address: mnowotny@iimcb.gov.pl.
International Institute of Molecular and Cell Biology · PLJohns Hopkins University · USInstitute of Biochemistry and Biophysics, Polish Academy of Sciences · PLPalacký University Olomouc · CZRegional Centre of Advanced Technologies and Materials · CZ

Funding

Single Molecule Study of Helicase MechanismsR01GM065367 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI HA, TAEKJIP · 2002 to 2014
$3.6M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM065367
6 · The paper itself

Abstract

HIV-1 reverse transcriptase (RT) possesses both DNA polymerase activity and RNase H activity that act in concert to convert single-stranded RNA of the viral genome to double-stranded DNA that is then integrated into the DNA of the infected cell. Reverse transcriptase-catalyzed reverse transcription critically relies on the proper generation of a polypurine tract (PPT) primer. However, the mechanism of PPT primer generation and the features of the PPT sequence that are critical for its recognition by HIV-1 RT remain unclear. Here, we used a chemical cross-linking method together with molecular dynamics simulations and single-molecule assays to study the mechanism of PPT primer generation. We found that the PPT was specifically and properly recognized within covalently tethered HIV-1 RT-nucleic acid complexes. These findings indicated that recognition of the PPT occurs within a stable catalytic complex after its formation. We found that this unique recognition is based on two complementary elements that rely on the PPT sequence: RNase H sequence preference and incompatibility of the poly(rA/dT) tract of the PPT with the nucleic acid conformation that is required for RNase H cleavage. The latter results from rigidity of the poly(rA/dT) tract and leads to base-pair slippage of this sequence upon deformation into a catalytically relevant geometry. In summary, our results reveal an unexpected mechanism of PPT primer generation based on specific dynamic properties of the poly(rA/dT) segment and help advance our understanding of the mechanisms in viral RNA reverse transcription.

Indexed as

Base SequenceCrystallography, X-RayDNA PrimersDNA, ViralHIV-1HIV Reverse TranscriptaseNucleic Acid ConformationNucleic AcidsPoly APolynucleotidesPoly UPurinesRibonuclease HRNA, ViralDNA PrimersDNA, ViralHIV Reverse TranscriptaseNucleic AcidsPoly APolynucleotidesPoly UPurinesreverse transcriptase, Human immunodeficiency virus 1Ribonuclease HRNA, Viralcysteine-mediated cross-linkinghuman immunodeficiency virus (HIV)molecular dynamicsnucleic acid structureprotein-nucleic acid interactionreverse transcriptaseribonuclease H

Identifiers

PMID29122886
PMCPMC5766924
OpenAlexW2767867248

What OpenQuestion holds

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LicenceCC BY
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.