Evidence map›Paper›PMID 25947153›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA.

Jan Hellert, Magdalena Weidner-Glunde, Joern Krausze, Heinrich Lünsdorf, Christiane Ritter, Thomas F Schulz, Thorsten Lührs

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

58 citing papers in PubMed, 75 citations in OpenAlex.

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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.

Jan HellertDepartment of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
Magdalena Weidner-GlundeInstitute of Virology, Hannover Medical School, 30625 Hannover, Germany; and.
Joern KrauszeDepartment of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
Heinrich LünsdorfCentral Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Christiane RitterDepartment of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
Thomas F SchulzInstitute of Virology, Hannover Medical School, 30625 Hannover, Germany; and Thorsten.Luhrs@SeNostic.com schulz.thomas@mh-hannover.de.
Thorsten LührsDepartment of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Institute of Virology, Hannover Medical School, 30625 Hannover, Germany; and Thorsten.Luhrs@SeNostic.com schulz.thomas@mh-hannover.de.
Helmholtz Centre for Infection Research · DEMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kaposi sarcoma herpesvirus (KSHV) persists as a latent nuclear episome in dividing host cells. This episome is tethered to host chromatin to ensure proper segregation during mitosis. For duplication of the latent genome, the cellular replication machinery is recruited. Both of these functions rely on the constitutively expressed latency-associated nuclear antigen (LANA) of the virus. Here, we report the crystal structure of the KSHV LANA DNA-binding domain (DBD) in complex with its high-affinity viral target DNA, LANA binding site 1 (LBS1), at 2.9 Å resolution. In contrast to homologous proteins such as Epstein-Barr virus nuclear antigen 1 (EBNA-1) of the related γ-herpesvirus Epstein-Barr virus, specific DNA recognition by LANA is highly asymmetric. In addition to solving the crystal structure, we found that apart from the two known LANA binding sites, LBS1 and LBS2, LANA also binds to a novel site, denoted LBS3. All three sites are located in a region of the KSHV terminal repeat subunit previously recognized as a minimal replicator. Moreover, we show that the LANA DBD can coat DNA of arbitrary sequence by virtue of a characteristic lysine patch, which is absent in EBNA-1 of the Epstein-Barr virus. Likely, these higher-order assemblies involve the self-association of LANA into supermolecular spirals. One such spiral assembly was solved as a crystal structure of 3.7 Å resolution in the absence of DNA. On the basis of our data, we propose a model for the controlled nucleation of higher-order LANA oligomers that might contribute to the characteristic subnuclear KSHV microdomains ("LANA speckles"), a hallmark of KSHV latency.

Indexed as

Amino Acid SequenceAntigens, ViralBase SequenceBinding SitesCrystallography, X-RayDNA-Binding ProteinsDNA, ViralHerpesvirus 8, HumanHumansModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNuclear ProteinsProtein Structure, QuaternaryProtein Structure, TertiaryScattering, Small AngleAntigens, ViralDNA-Binding ProteinsDNA, Virallatency-associated nuclear antigenNuclear ProteinsDNA-binding proteingammaherpesvirinaeKSHV LANAviral latencyX-ray crystallography

Identifiers

PMID25947153
PMCPMC4450395
OpenAlexW1579734686

What OpenQuestion holds

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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.