Evidence map›Paper›PMID 26895240›Full record

ArticlePLoS pathogens2016

Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface.

Valerie J Klema, Mengyi Ye, Aditya Hindupur, Tadahisa Teramoto, Keerthi Gottipati, Radhakrishnan Padmanabhan, Kyung H Choi

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
15.1field-weighted citation impact, top 1% 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

68 citing papers in PubMed, 132 citations in OpenAlex.

  1. Article
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  7. Article
  8. Review
  9. Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025
    Review
  18. Article
  19. Review
  20. Article

8 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Valerie J KlemaDepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
Mengyi YeDepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
Aditya HindupurDepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
Tadahisa TeramotoDepartment of Microbiology and Immunology, Georgetown University School of Medicine, Washington, D.C., United States of America.
Keerthi GottipatiDepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
Radhakrishnan PadmanabhanDepartment of Microbiology and Immunology, Georgetown University School of Medicine, Washington, D.C., United States of America.
Kyung H ChoiDepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
The University of Texas Medical Branch at Galveston · USGeorgetown University · US

Funding

MECHANISM OF RNA SYNTHESIS BY DENGUE VIRUS NS5R01AI087856 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Kyung H Choi · 2011 to 2026
$5.5M
NIAID NIH HHS R01 AI087856
6 · The paper itself

Abstract

Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quaternary organization of the functional enzyme are available. We report the crystal structure of dengue virus full-length NS5, where eight molecules of NS5 are arranged as four independent dimers in the crystallographic asymmetric unit. The relative orientation of each monomer within the dimer, as well as the orientations of the MTase and RdRp domains within each monomer, is conserved, suggesting that these structural arrangements represent the biologically relevant conformation and assembly of this multi-functional enzyme. Essential interactions between MTase and RdRp domains are maintained in the NS5 dimer via inter-molecular interactions, providing evidence that flavivirus NS5 can adopt multiple conformations while preserving necessary interactions between the MTase and RdRp domains. Furthermore, many NS5 residues that reduce viral replication are located at either the inter-domain interface within a monomer or at the inter-molecular interface within the dimer. Hence the X-ray structure of NS5 presented here suggests that MTase and RdRp activities could be coordinated as a dimer during viral genome replication.

Indexed as

Protein MultimerizationDengue VirusMethyltransferasesProtein Structure, TertiaryRNA-Dependent RNA PolymeraseViral Nonstructural ProteinsVirus ReplicationMethyltransferasesNS5 protein, dengue virusRNA-Dependent RNA PolymeraseViral Nonstructural Proteins

Identifiers

PMID26895240
PMCPMC4760774
OpenAlexW2281975422

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.