title: The Roles of Histidines and Charged Residues as Potential Triggers of a Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein.
abstract: 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.
authors.affiliation: Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, Virginia 22908, United States of America.|Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, United States of America.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, Virginia 22908, United States of America.|Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, United States of America.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Gregory
authors.affiliation: Department Cell Biology, University of Virginia, Charlottesville, Virginia 22908, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Nelson
authors.affiliation: Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, Virginia 22908, United States of America.|Department Cell Biology, University of Virginia, Charlottesville, Virginia 22908, United States of America.
authors.forename: Judith M
authors.initials: JM
authors.lastname: White
authors.affiliation: Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, Virginia 22908, United States of America.|Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, United States of America.
authors.forename: Lukas K
authors.initials: LK
authors.lastname: Tamm
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D029043:Ebolavirus / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D006639:Histidine