UniProtKB Q05320 (VGP_EBOZM) flat file, Envelope glycoprotein, Zaire ebolavirus (strain Mayinga-76)
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The trimeric GP1,2 spike mediates entry, with GP1 binding the receptor and GP2 fusing the membranes
"Trimeric GP1,2 complexes form the virion surface spikes and mediate the viral entry processes, with GP1 acting as the receptor-binding subunit and GP2 as the membrane fusion subunit."
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Endosomal cathepsin B and L remove the GP1 glycan cap, allowing GP1 to bind the entry receptor NPC1
"proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L removes the glycan cap and allows GP1 binding to the host entry receptor NPC1"
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ADAM17 cleavage removes the GP2 transmembrane anchor and releases shed GP1,2 delta complexes
"Proteolytic processing of GP1,2 by host ADAM17 can remove the transmembrane anchor of GP2 and leads to shedding of complexes consisting in GP1 and truncated GP2 (GP1,2delta)"
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GP localises to plasma-membrane lipid rafts, the probable assembly and budding site
"In the cell, localizes to the plasma membrane lipid rafts, which probably represent the assembly and budding site."
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The GP gene yields GP, sGP and ssGP by RNA editing, with sGP and ssGP held as separate UniProt entries
"The unedited RNA gives rise to the small secreted glycoprotein sGP (AC P60170), the +2A edited RNA gives rise to the super small secreted glycoprotein ssGP (AC Q9YMG2)."
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses.
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Transfected Ebola and Marburg GP partition into lipid raft fractions, while a GP mutated at the palmitoylation sites C670/C672 does not
"As shown in Fig. 1 A and B, a significant fraction of Ebola and Marburg GPs were found to reside in rafts."
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Raft association of GP is cholesterol-dependent
"resulted in almost complete removal of Ebola GP from rafts"
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GP colocalises with the raft marker GM1 in large plasma-membrane patches on intact cells
"a substantial portion of both of the GPs were found to colocalize with GM1 in large patches on the plasma membrane"
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Coexpression of GP with VP40 directs both proteins into released particles
"coexpression of GPwt and VP40, directed the majority of both proteins into the supernatant"
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GP-containing virus-like particles are released through discrete plasma-membrane platforms
"where a large number of particles that stain for GP exit through a small region of the plasma membrane"
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The spikes on released particles are GP, shown by immunogold staining
"Immunogold staining of the VLPs with anti-Ebola GP antibodies demonstrated the identity of the spikes on the surface of the particles as Ebola GP"
Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells.
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Adenovirus-delivered Ebola GP causes primary human cardiac microvascular endothelial cells to lose adhesion and die
"Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death."
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The cytotoxic effect requires intracellular GP expression and is not transferred by conditioned medium
"suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect"
Ectodomain shedding of the glycoprotein GP of Ebola virus.
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ADAM17/TACE cleavage at D637 removes the transmembrane anchor and liberates soluble GP1 plus truncated GP2 complexes from the cell surface
"Proteolytic cleavage taking place at amino-acid position D637 removes the transmembrane anchor and liberates complexes consisting of GP1 and truncated GP2 (GP(2delta)) subunits from the cell surface."
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Shed GP circulates in infected animals and blocks virus-neutralising antibodies
"shed GP is present in significant amounts in the blood of virus-infected animals"
Structure of the Ebola fusion peptide in a membrane-mimetic environment and the interaction with lipid rafts.
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The GP2 fusion peptide interacts with the host membrane and leads to membrane fusion
"This region interacts with the cellular membrane of the host and leads to membrane fusion."
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The fusion peptide interacts with detergent-resistant membrane fractions, with Trp8 and Phe12 required for its structure in the bilayer
"EBO(16) can interact with detergent-resistant membrane fractions"
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The peptide structure was determined in SDS micelles and detergent-resistant membranes, not with defined lipids
"insertion of the peptide was modeled by experiments in which the tryptophan fluorescence and (1)H NMR were monitored in the presence of sodium dodecyl sulfate micelles or in the presence of detergent-resistant membrane fractions"
Ebola virus uses clathrin-mediated endocytosis as an entry pathway.
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Four independent perturbations of the clathrin pathway block EbGP-mediated entry without affecting wild-type HIV or VSVg-pseudotyped HIV
"Inhibition of clathrin pathway using dominant-negative Eps15, siRNA-mediated knockdown of clathrin heavy chain, chlorpromazine and sucrose blocked EbGP pseudotyped HIV infection."
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Chlorpromazine and bafilomycin A1 also block entry of replication-competent Ebola virus, so entry is clathrin- and pH-dependent
"Also, both chlorpromazine and Bafilomycin A1 inhibited entry of infectious EBOV."
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The study's stated aim and conclusion concern the endocytic route of entry, not the localisation of the glycoprotein
"In this study we examined whether EBOV requires the clathrin-mediated endocytic pathway for entry."
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The authors allow that Ebola virus may use additional entry routes in other settings
"it is also possible that EBOV could utilize other entry pathways in addition to clathrin-mediated endocytosis under different circumstances"
Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum.
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Transiently expressed full-length GP colocalises with a DsRed2-ER marker
"Co-expression of Ebola GP with DsRed2-ER showed that GP had localized within the ER (Figure 1B)."
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GP lacking the mucin-like region does not accumulate in the endoplasmic reticulum
"it did not accumulate in the ER (Figure 2A)"
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GP was not detected in the Golgi or in early or late endosomes in this assay
"Notably, GP was not found within late endosomes (Figure 1B), Golgi or early endosomes (data not shown)."
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Other studies place GP at the plasma membrane in infected non-human primate tissue and in HeLa cells
"However, separate studies show that Ebola GP localizes in the plasma membrane of either tissues from experimentally infected non-human primates"
Shed GP of Ebola virus triggers immune activation and increased vascular permeability.
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Shed GP binds and activates uninfected dendritic cells and macrophages, inducing cytokine secretion
"In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines"
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Secreted sGP does not activate dendritic cells or macrophages, so the activity is specific to shed GP
"Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs."
Structural and molecular basis for Ebola virus neutralization by protective human antibodies.
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GP is a class I fusion protein whose disulfide-linked GP1 and GP2 subunits assemble into a chalice-shaped trimer
"The EBOV glycoprotein (GP) is a class I fusion protein comprising disulfide-linked subunits, GP1 and GP2, which associate to form a chalice-shaped"
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GP1 binds the entry receptor NPC1, allowing GP2-mediated fusion of the viral and host membranes
"The GP1 subunit binds to the EBOV receptor, Niemann-Pick C1 (NPC1), allowing GP2-mediated fusion of the viral and host-cell membranes"
Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection.
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GP binds CD4+ T cells through TLR4 and kills them without infecting them
"Using immunoprecipitation assays and flow cytometry, we demonstrate that EBOV directly binds to CD4+ T cells through interaction of GP with TLR4."
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TLR4 inhibition rescues GP-induced CD4+ T cell death
"The addition of the TLR4 inhibitor CLI-095 significantly reduced CD4+ T cell death induced by GP."
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GP also drives monocyte differentiation, which raises their susceptibility to infection
"stimulation with EBOV or GP augments monocyte maturation as determined by an overall increase in expression levels of markers of differentiation"
Ebola Virus Shed Glycoprotein Triggers Differentiation, Infection, and Death of Monocytes Through Toll-Like Receptor 4 Activation.
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Soluble shed GP drives monocyte differentiation, infection and death
"treatment of monocytic cells with Ebola virus shed glycoprotein (GP) promotes their differentiation resulting in increased infection and cell death"
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The effects of shed GP require the TLR4 pathway
"The effects were inhibited by blocking Toll-like receptor 4 pathway."