Evidence map›Paper›PMID 26511021›Full record

ArticleThe EMBO journal2015

Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex.

Ming F Lye, Mayuri Sharma, Kamel El Omari, David J Filman, Jonathan P Schuermann, James M Hogle, Donald M Coen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
5.5field-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

51 citing papers in PubMed, 73 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 3 institutions in 2 countries.

Ming F LyeDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Mayuri SharmaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Kamel El OmariDivision of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Headington Oxford, UK.
David J FilmanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Jonathan P SchuermannNortheastern Collaborative Access Team, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
James M HogleDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA james_hogle@hms.harvard.edu don_coen@hms.harvard.edu.
Donald M CoenDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA james_hogle@hms.harvard.edu don_coen@hms.harvard.edu.
Harvard University · USCornell University · USUniversity of Oxford · GB

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Human Cytomegalovirus Nuclear Egress: Molecular Mechanisms and Drug TargetingR01AI026077 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI COEN, DONALD M · 1999 to 2019
$10.9M
NIAID NIH HHS R01 AI026077NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

Herpesvirus nucleocapsids escape from the nucleus in a process orchestrated by a highly conserved, viral nuclear egress complex. In human cytomegalovirus, the complex consists of two proteins, UL50 and UL53. We solved structures of versions of UL53 and the complex by X-ray crystallography. The UL53 structures, determined at 1.93 and 3.0 Å resolution, contained unexpected features including a Bergerat fold resembling that found in certain nucleotide-binding proteins, and a Cys3His zinc finger. Substitutions of zinc-coordinating residues decreased UL50-UL53 co-localization in transfected cells, and, when incorporated into the HCMV genome, ablated viral replication. The structure of the complex, determined at 2.47 Å resolution, revealed a mechanism of heterodimerization in which UL50 clamps onto helices of UL53 like a vise. Substitutions of particular residues on the interaction interface disrupted UL50-UL53 co-localization in transfected cells and abolished virus production. The structures and the identification of contacts can be harnessed toward the rational design of novel and highly specific antiviral drugs and will aid in the detailed understanding of nuclear egress.

Indexed as

Crystallography, X-RayGenome, ViralHerpesviridaeProtein Structure, SecondaryViral ProteinsVirus ReplicationUL53 protein, Human herpesvirus 1Viral ProteinsBergerat foldcrystal structureinteraction interfacenuclear egress complexzinc finger

Identifiers

PMID26511021
PMCPMC4687685
OpenAlexW1830479122

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.