Evidence map›Paper›PMID 24227840›Full record

ArticleJournal of virology2014

Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface.

Katrin Mücke, Christina Paulus, Katharina Bernhardt, Katrin Gerrer, Kathrin Schön, Alina Fink, Eva-Maria Sauer, Alexandra Asbach-Nitzsche, Thomas Harwardt, Bärbel Kieninger and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

33 citing papers in PubMed, 42 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

13 authors at 2 institutions in 1 country.

Katrin MückeInstitute for Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
Christina Paulus
Katharina Bernhardt
Katrin Gerrer
Kathrin Schön
Alina Fink
Eva-Maria Sauer
Alexandra Asbach-Nitzsche
Thomas Harwardt
Bärbel Kieninger
Werner Kremer
Hans Robert Kalbitzer
Michael Nevels
University of Regensburg · DEInstitute of Medical Microbiology and Hygiene · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study, we identify the cellular chromosome receptor for IE1. We demonstrate that the viral protein targets human nucleosomes by directly binding to core histones in a nucleic acid-independent manner. IE1 exhibits two separable histone-interacting regions with differential binding specificities for H2A-H2B and H3-H4. The H2A-H2B binding region was mapped to an evolutionarily conserved 10-amino-acid motif within the chromatin-tethering domain (CTD) of IE1. Results from experimental approaches combined with molecular modeling indicate that the IE1 CTD adopts a β-hairpin structure, docking with the acidic pocket formed by H2A-H2B on the nucleosome surface. IE1 binds to the acidic pocket in a way similar to that of the latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus. Consequently, the IE1 and LANA CTDs compete for binding to nucleosome cores and chromatin. Our work elucidates in detail how a key viral regulator is anchored to human chromosomes and identifies the nucleosomal acidic pocket as a joint target of proteins from distantly related viruses. Based on the striking similarities between the IE1 and LANA CTDs and the fact that nucleosome targeting by IE1 is dispensable for productive replication even in "clinical" strains of hCMV, we speculate that the two viral proteins may serve analogous functions during latency of their respective viruses.

Indexed as

Amino Acid SequenceBinding SitesChromosomes, HumanCytomegalovirusCytomegalovirus InfectionsHistonesHumansImmediate-Early ProteinsModels, MolecularMolecular Sequence DataNucleosomesProtein BindingProtein Structure, TertiaryHistonesIE1 protein, cytomegalovirusImmediate-Early ProteinsNucleosomes

Identifiers

PMID24227840
PMCPMC3911650
OpenAlexW2054989124

What OpenQuestion holds

Textmetadata
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.