Evidence map›Paper›PMID 25969444›Full record

ArticleNucleic acids research2015

Structural and sequencing analysis of local target DNA recognition by MLV integrase.

Sriram Aiyer, Paolo Rossi, Nirav Malani, William M Schneider, Ashwin Chandar, Frederic D Bushman, Gaetano T Montelione, Monica J Roth

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. The Integrase: An Overview of a Key Player Enzyme in the Antiviral Scenario.International journal of molecular sciences · 2023
    Review
  4. Review
  5. Article
  6. Structure and function of retroviral integrase.Nature reviews. Microbiology · 2022
    Review
  7. Article
  8. Article
  9. Foamy Virus Integrase in Development of Viral Vector for Gene Therapy.Journal of microbiology and biotechnology · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Retroviral DNA Integration.Chemical reviews · 2016
    Review
  16. Article
  17. Article
  18. Article
  19. Sites of retroviral DNA integration: From basic research to clinical applications.Critical reviews in biochemistry and molecular biology · 2016
    Review
  20. Multifunctional facets of retrovirus integrase.World journal of biological chemistry · 2015
    Review
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

8 authors at 3 institutions in 1 country.

Sriram AiyerDepartment of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Paolo RossiCenter for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, and Northeast Structural Genomics Consortium (NESG), Rutgers University, Piscataway, NJ 08854, USA.
Nirav MalaniDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
William M SchneiderDepartment of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ 08854, USA.
Ashwin ChandarDepartment of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway, NJ 08854, USA.
Frederic D BushmanDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gaetano T MontelioneCenter for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, and Northeast Structural Genomics Consortium (NESG), Rutgers University, Piscataway, NJ 08854, USA Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Monica J RothDepartment of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA roth@rwjms.rutgers.edu.
Johnson University · USUniversity of Pennsylvania · USJoint Center for Structural Genomics · US

Funding

University of Georgia ProjectU54GM094597 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI MONTELIONE, GAETANO T · 2010 to 2014
$36.9M
Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
Integration of Murine Retroviral VectorsR01GM070837 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2005 to 2013
$2.1M
Retroviral Integration & HDAC inhibitorsR01GM088808 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2009 to 2012
$1.3M
NIAID NIH HHS R01 AI 052845NIGMS NIH HHS 1R01GM088808NIGMS NIH HHS GM070837NIGMS NIH HHS R01 GM070837NIGMS NIH HHS R01 GM088808NIGMS NIH HHS U54-GM094597
6 · The paper itself

Abstract

Target-site selection by retroviral integrase (IN) proteins profoundly affects viral pathogenesis. We describe the solution nuclear magnetic resonance structure of the Moloney murine leukemia virus IN (M-MLV) C-terminal domain (CTD) and a structural homology model of the catalytic core domain (CCD). In solution, the isolated MLV IN CTD adopts an SH3 domain fold flanked by a C-terminal unstructured tail. We generated a concordant MLV IN CCD structural model using SWISS-MODEL, MMM-tree and I-TASSER. Using the X-ray crystal structure of the prototype foamy virus IN target capture complex together with our MLV domain structures, residues within the CCD α2 helical region and the CTD β1-β2 loop were predicted to bind target DNA. The role of these residues was analyzed in vivo through point mutants and motif interchanges. Viable viruses with substitutions at the IN CCD α2 helical region and the CTD β1-β2 loop were tested for effects on integration target site selection. Next-generation sequencing and analysis of integration target sequences indicate that the CCD α2 helical region, in particular P187, interacts with the sequences distal to the scissile bonds whereas the CTD β1-β2 loop binds to residues proximal to it. These findings validate our structural model and disclose IN-DNA interactions relevant to target site selection.

Indexed as

Catalytic DomainDNAIntegrasesModels, MolecularMoloney murine leukemia virusMutationProtein BindingProtein Structure, TertiarySequence Analysis, DNAViral ProteinsDNAIntegrasesViral Proteins

Identifiers

PMID25969444
PMCPMC4477651
OpenAlexW1602453169

What OpenQuestion holds

Textmetadata
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.