Evidence map›Paper›PMID 26424851›Full record

ArticleNucleic acids research2015

KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA.

Rajesh Ponnusamy, Maxim V Petoukhov, Bruno Correia, Tania F Custodio, Franceline Juillard, Min Tan, Marta Pires de Miranda, Maria A Carrondo, J Pedro Simas, Kenneth M Kaye and 2 more

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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.2field-weighted citation impact, top 13% 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, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Molecular Mechanisms of KSHV Latency Establishment and Maintenance.Current clinical microbiology reports · 2024
    Article
  5. Article
  6. KSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistence.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  7. Review
  8. Article
  9. Journal of virology · 2018
    Article
  10. Superresolution microscopy reveals structural mechanisms driving the nanoarchitecture of a viral chromatin tether.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Kaposi's Sarcoma Herpesvirus Genome Persistence.Frontiers in microbiology · 2016
    Review
  17. KSHV Genome Replication and Maintenance.Frontiers in microbiology · 2016
    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

12 authors at 5 institutions in 3 countries.

Rajesh PonnusamyInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2700-157, Portugal.
Maxim V PetoukhovEuropean Molecular Biology Laboratory, Hamburg Unit, EMBL c/o DESY, Hamburg 22607, Germany.
Bruno CorreiaInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2700-157, Portugal.
Tania F CustodioInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2700-157, Portugal.
Franceline JuillardDepartments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Min TanDepartments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Marta Pires de MirandaInstituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.
Maria A CarrondoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2700-157, Portugal.
J Pedro SimasInstituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.
Kenneth M KayeDepartments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Dmitri I SvergunEuropean Molecular Biology Laboratory, Hamburg Unit, EMBL c/o DESY, Hamburg 22607, Germany.
Colin E McVeyInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2700-157, Portugal mcvey@itqb.unl.pt.
Universidade Nova de Lisboa · PTBrigham and Women's Hospital · USEuropean Molecular Biology Laboratory · DEUniversity of Lisbon · PTHarvard University · US

Funding

GENETIC AND BIOCHEMICAL STUDIES OF THE KSHV LANA GENER01CA082036 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KAYE, KENNETH M · 1999 to 2019
$7.6M
KSHV Latent Infection ReplicationR01DE025208 · NIDCR · BRIGHAM AND WOMEN'S HOSPITAL · PI KAYE, KENNETH M · 2015 to 2025
$5.3M
NCI NIH HHS CA082036NCI NIH HHS R01 CA082036NIDCR NIH HHS DE025208NIDCR NIH HHS R01 DE025208
6 · The paper itself

Abstract

Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of γ2-herpesviruses. LANA binds cooperatively to the terminal repeat (TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using strikingly different modes. Solution structure of LANA complexes revealed that while kLANA tetramer is intrinsically bent both in the free and bound state to LBS1-2 DNA, mLANA oligomers instead adopt a rigid linear conformation. In addition, we report a novel non-ring kLANA structure that displays more flexibility at its assembly interface than previously demonstrated. We identified a hydrophobic pivot point located at the dimer-dimer assembly interface, which gives rotational freedom for kLANA to adopt variable conformations to accommodate both LBS1-2 and LBS2-1-3 DNA. Alterations in the arrangement of LBS within TR or at the tetramer assembly interface have a drastic effect on the ability of kLANA binding. We also show kLANA and mLANA DNA binding functions can be reciprocated. Although KSHV and MHV-68 are closely related, the findings provide new insights into how the structure, oligomerization, and DNA binding of LANA have evolved differently to assemble on the TR DNA.

Indexed as

Herpesvirus 8, HumanRhadinovirusAntigens, ViralBinding SitesDNA, ViralModels, MolecularMutationNuclear ProteinsNucleic Acid ConformationProtein BindingProtein MultimerizationProtein Structure, TertiaryTerminal Repeat SequencesThermodynamicsAntigens, ViralDNA, Virallatency-associated nuclear antigenNuclear Proteins

Identifiers

PMID26424851
PMCPMC4787769
OpenAlexW1674548589

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.