Evidence map›Paper›PMID 26037594›Full record

ArticleeLife2015

Asymmetric conformational maturation of HIV-1 reverse transcriptase.

Xunhai Zheng, Lalith Perera, Geoffrey A Mueller, Eugene F DeRose, Robert E London

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 18% 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, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016
    Pooled it
  2. Protease-mediated maturation of M-PMV reverse transcriptase into a functional heterodimer.Protein science : a publication of the Protein Society · 2026
    Article
  3. Article
  4. Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer.Protein science : a publication of the Protein Society · 2022
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
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

5 authors at 2 institutions in 1 country.

Xunhai ZhengGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States.
Lalith PereraGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States.
Geoffrey A MuellerGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States.
Eugene F DeRoseGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States.
Robert E LondonGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States.
National Institutes of Health · USNational Institute of Environmental Health Sciences · US

Funding

Aids Related Nmr ResearchZIAES050147 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, ROBERT E · 2009 to 2020
$6.3M
Macromolecular ModelingZICES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 2012 to 2025
$5.7M
DESIGN, SYNTHESIS &NMR CHARACTERIZATION OF FLUORINATED HIV PROTEASE INHIBITORZ01ES050147 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, ROBERT E · 1995 to 2008
$2.3M
Intramural NIH HHS Z01 ES050147PHS HHS HHSN273200700046U
6 · The paper itself

Abstract

HIV-1 reverse transcriptase utilizes a metamorphic polymerase domain that is able to adopt two alternate structures that fulfill catalytic and structural roles, thereby minimizing its coding requirements. This ambiguity introduces folding challenges that are met by a complex maturation process. We have investigated this conformational maturation using NMR studies of methyl-labeled RT for the slower processes in combination with molecular dynamics simulations for rapid processes. Starting from an inactive conformation, the p66 precursor undergoes a unimolecular isomerization to a structure similar to its active form, exposing a large hydrophobic surface that facilitates initial homodimer formation. The resulting p66/p66' homodimer exists as a conformational heterodimer, after which a series of conformational adjustments on different time scales can be observed. Formation of the inter-subunit RH:thumb' interface occurs at an early stage, while maturation of the connection' and unfolding of the RH' domains are linked and occur on a much slower time scale.

Indexed as

Models, MolecularChromatography, GelDimerizationHIV-1HIV Reverse TranscriptaseMolecular Dynamics SimulationNuclear Magnetic Resonance, BiomolecularProtein ConformationProtein FoldingHIV Reverse Transcriptasereverse transcriptase, Human immunodeficiency virus 1biophysicsDNA repairHIV-1 reverse transcriptasehumanmouseNMRstructural biologyviruses

Identifiers

PMID26037594
PMCPMC4452869
OpenAlexW1910058964

What OpenQuestion holds

Textmetadata
LicenceCC0
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.