Evidence map›Paper›PMID 27035968›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B.

Tzviya Zeev-Ben-Mordehai, Daven Vasishtan, Anna Hernández Durán, Benjamin Vollmer, Paul White, Arun Prasad Pandurangan, C Alistair Siebert, Maya Topf, Kay Grünewald

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
–field-weighted citation impact
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

72 citing papers in PubMed.

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  6. Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.Proceedings of the National Academy of Sciences of the United States of America · 2024
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12 more citing papers are in PubMed but not listed here.

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

9 authors.

Tzviya Zeev-Ben-MordehaiOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
Daven VasishtanOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
Anna Hernández DuránOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, London WC1E 7HX, United Kingdom.
Benjamin VollmerOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
Paul WhiteOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
Arun Prasad PanduranganInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, London WC1E 7HX, United Kingdom.
C Alistair SiebertOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
Maya TopfInstitute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, London WC1E 7HX, United Kingdom.
Kay GrünewaldOxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; kay@strubi.ox.ac.uk.ORCID http://orcid.org/0000-0002-4788-2691

Funding

Medical Research Council G0600084Medical Research Council MR/M019292/1Wellcome Trust
6 · The paper itself

Abstract

Many viruses are enveloped by a lipid bilayer acquired during assembly, which is typically studded with one or two types of glycoproteins. These viral surface proteins act as the primary interface between the virus and the host. Entry of enveloped viruses relies on specialized fusogen proteins to help merge the virus membrane with the host membrane. In the multicomponent herpesvirus fusion machinery, glycoprotein B (gB) acts as this fusogen. Although the structure of the gB ectodomain postfusion conformation has been determined, any other conformations (e.g., prefusion, intermediate conformations) have so far remained elusive, thus restricting efforts to develop antiviral treatments and prophylactic vaccines. Here, we have characterized the full-length herpes simplex virus 1 gB in a native membrane by displaying it on cell-derived vesicles and using electron cryotomography. Alongside the known postfusion conformation, a novel one was identified. Its structure, in the context of the membrane, was determined by subvolume averaging and found to be trimeric like the postfusion conformation, but appeared more condensed. Hierarchical constrained density-fitting of domains unexpectedly revealed the fusion loops in this conformation to be apart and pointing away from the anchoring membrane. This vital observation is a substantial step forward in understanding the complex herpesvirus fusion mechanism, and opens up new opportunities for more targeted intervention of herpesvirus entry.

Indexed as

Cryoelectron MicroscopyHerpesvirus 1, HumanMembrane GlycoproteinsProtein ConformationViral Envelope ProteinsMembrane GlycoproteinsViral Envelope Proteinsclass III viral fusion proteinelectron cryotomographymembrane fusionprefusion conformationsubvolume averaging

Identifiers

PMID27035968
PMCPMC4839410

What OpenQuestion holds

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Registered trials

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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.