Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2

Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-07, Vol.108 (27), p.11211-11216
Main Authors: Gregory, Sonia M, Harada, Erisa, Liang, Binyong, Delos, Sue E, White, Judith M, Tamm, Lukas K
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biological Sciences
cathepsins
Cell membranes
Circular Dichroism
circular dichroism spectroscopy
Crystal structure
Disulfides
Ebola virus
Ebolavirus
Ebolavirus - genetics
Ebolavirus - pathogenicity
Ebolavirus - physiology
fever
Glycoproteins
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
hydrophobicity
Lipids
Liposomes
membrane fusion
Membranes
Micelles
Models, Molecular
Molecular Sequence Data
nuclear magnetic resonance spectroscopy
Nuclear Magnetic Resonance, Biomolecular
Primates
Protein Structure, Secondary
Proteins
Viral Envelope Proteins - chemistry
Viral Envelope Proteins - genetics
Viral Envelope Proteins - physiology
Viral fusion proteins
virion
Virus Internalization
Viruses
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Summary:Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH [less-than or equal to]5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1104760108