The Roles of Histidines and Charged Residues as Potential Triggers of a Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein
| Autor: | Elizabeth A. Nelson, Lukas K. Tamm, Jinwoo Lee, Sonia M. Gregory, Judith M. White |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Conformational change Magnetic Resonance Spectroscopy Cell Membranes lcsh:Medicine Spectrum analysis techniques medicine.disease_cause Membrane Fusion Biochemistry Protein Structure Secondary Cell Fusion Protein structure Viral Envelope Proteins Amino Acids lcsh:Science Multidisciplinary Cell fusion Organic Compounds Chemistry Circular Dichroism Neurochemistry Neurotransmitters Hydrogen-Ion Concentration Ebolavirus Lipids Physical Sciences Cellular Structures and Organelles Glutamate Basic Amino Acids Research Article Cell Physiology Viral Entry Endosome Recombinant Fusion Proteins Molecular Sequence Data Microbiology Structure-Activity Relationship 03 medical and health sciences NMR spectroscopy Viral entry Virology medicine Histidine Vesicles Amino Acid Sequence Ebola virus Organic Chemistry lcsh:R Chemical Compounds Biology and Life Sciences Proteins Lipid bilayer fusion Cell Biology Research and analysis methods 030104 developmental biology NMR relaxation Liposomes Biophysics lcsh:Q Sequence Alignment Viral Transmission and Infection Neuroscience |
| Zdroj: | PLOS ONE PLoS ONE, Vol 11, Iss 3, p e0152527 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0152527 |
| Popis: | Ebola virus (EBOV) enters cells from late endosomes/lysosomes under mildly acidic conditions. Entry by fusion with the endosomal membrane requires the fusion loop (FL, residues 507-560) of the EBOV surface glycoprotein to undergo a pH-dependent conformational change. To find the pH trigger for this reaction we mutated multiple conserved histidines and charged and uncharged hydrophilic residues in the FL and measured their activity by liposome fusion and cell entry of virus-like particles. The FL location in the membrane was assessed by NMR using soluble and lipid-bound paramagnetic relaxation agents. While we could not identify a single residue to be alone responsible for pH triggering, we propose that a distributed pH effect over multiple residues induces the conformational change that enhances membrane insertion and triggers the fusion activity of the EBOV FL. |
| Databáze: | OpenAIRE |
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