ArticleThe Journal of biological chemistry2018
Mechanism of polypurine tract primer generation by HIV-1 reverse transcriptase.
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.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Structural Basis of Polypurine Track Strand Displacement by HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Expression of HIV from a 1-LTR circular DNA in the absence of integration.Retrovirology · 2025Article
- Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes.Journal of chemical theory and computation · 2024Article
- May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription.International journal of molecular sciences · 2024Review
- Structural and computational studies of HIV-1 RNA.RNA biology · 2024Review
- HIV-1 3'-Polypurine Tract Mutations Confer Dolutegravir Resistance by Switching to an Integration-Independent Replication Mechanism via 1-LTR Circles.Journal of virology · 2023Article
- Structural basis of R-loop recognition by the S9.6 monoclonal antibody.Nature communications · 2022Article
- Article
- Role of salt-bridging interactions in recognition of viral RNA by arginine-rich peptides.Biophysical journal · 2021Article
- HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Distinct Retrotransposon Evolution Profile in the Genome of Rabbit (Oryctolagus cuniculus).Genome biology and evolution · 2021Article
- Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction.Viruses · 2021Article
- GC-Content Dependence of Elastic and Overstretching Properties of DNA:RNA Hybrid Duplexes.Biophysical journal · 2020Article
- RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution.Nature communications · 2019Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
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.
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