Evidence map›Paper›PMID 32040508›Full record

ArticlePLoS biology2020

Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding.

Dibyendu Kumar Das, Uriel Bulow, William E Diehl, Natasha D Durham, Fernando Senjobe, Kartik Chandran, Jeremy Luban, James B Munro

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
1.6field-weighted citation impact, top 9% 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

64 citing papers in PubMed, 92 citations in OpenAlex.

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4 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

8 authors at 3 institutions in 2 countries.

Dibyendu Kumar DasDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.
Uriel BulowDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.ORCID 0000-0003-4119-3171
William E DiehlProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-7943-1214
Natasha D DurhamDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.
Fernando SenjobeDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.ORCID 0000-0003-4322-6571
Kartik ChandranDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Jeremy LubanProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-5650-4054
James B MunroDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, United States of America.ORCID 0000-0001-7634-4633
Tufts University · USUniversity of Massachusetts Chan Medical School · USAlbert Einstein College of Medicine · US

Funding

Tufts Post-Baccalaureate Research Education ProgramR25GM066567 · NIGMS · TUFTS UNIVERSITY BOSTON · PI RIOS, MARIBEL · 2002 to 2024
$5.7M
Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variantR01AI148784 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUBAN, JEREMY · 2020 to 2024
$4.1M
Structural dynamics of single Ebolavirus GP molecules.DP2AI124384 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MUNRO, JAMES B · 2015 to 2015
$2.5M
Host-virus interactions in the control of filovirus entryR01AI134824 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CHANDRAN, KARTIK · 2018 to 2021
$1.9M
NIAID NIH HHS DP2 AI124384NIAID NIH HHS R01 AI134824NIAID NIH HHS R01 AI148784NIGMS NIH HHS R25 GM066567
6 · The paper itself

Abstract

The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry. How this interaction translates to GP2 domain-mediated fusion of viral and endosomal membranes is not known. Here, using a bulk fluorescence dequenching assay and single-molecule Förster resonance energy transfer (smFRET)-imaging, we found that acidic pH, Ca2+, and NPC1 binding synergistically induce conformational changes in GP2 and permit virus-liposome lipid mixing. Acidic pH and Ca2+ shifted the GP2 conformational equilibrium in favor of an intermediate state primed for NPC1 binding. Glycan cap cleavage on GP1 enabled GP2 to transition from a reversible intermediate to an irreversible conformation, suggestive of the postfusion 6-helix bundle; NPC1 binding further promoted transition to the irreversible conformation. Thus, the glycan cap of GP1 may allosterically protect against inactivation of EBOV by premature triggering of GP2.

Indexed as

Membrane FusionAllosteric RegulationCalciumEbolavirusFluorescence Resonance Energy TransferHEK293 CellsHumansHydrogen-Ion ConcentrationIntracellular Signaling Peptides and ProteinsNiemann-Pick C1 ProteinPolysaccharidesProtein BindingProtein ConformationProtein DomainsViral Envelope ProteinsVirus InternalizationCalciumenvelope glycoprotein, Ebola virusIntracellular Signaling Peptides and ProteinsNiemann-Pick C1 ProteinNPC1 protein, humanPolysaccharidesViral Envelope Proteins

Identifiers

PMID32040508
PMCPMC7034923
OpenAlexW3004859799

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.