title: The Ebola virus matrix protein deeply penetrates the plasma membrane: an important step in viral egress.
abstract: Ebola virus, from the Filoviridae family has a high fatality rate in humans and nonhuman primates and to date, to the best of our knowledge, has no FDA approved vaccines or therapeutics. Viral protein 40 (VP40) is the major Ebola virus matrix protein that regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of VP40 membrane binding that are important for viral release remain to be elucidated. In this study, we used fluorescence quenching of a tryptophan on the membrane-binding interface with brominated lipids along with mutagenesis of VP40 to understand the depth of membrane penetration into lipid bilayers. Experimental results indicate that VP40 penetrates 8.1 Å into the hydrocarbon core of the plasma membrane bilayer. VP40 also induces substantial changes to membrane curvature as it tubulates liposomes and induces vesiculation into giant unilamellar vesicles, effects that are abrogated by hydrophobic mutations. This is a critical step in viral egress as cellular assays demonstrate that hydrophobic residues that penetrate deeply into the plasma membrane are essential for plasma membrane localization and virus-like particle formation and release from cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, Indiana, USA.
authors.forename: Smita P
authors.initials: SP
authors.lastname: Soni
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Adu-Gyamfi
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: Yong
authors.forename: Clara S
authors.initials: CS
authors.lastname: Jee
authors.forename: Robert V
authors.initials: RV
authors.lastname: Stahelin
mesh_terms: D000595:Amino Acid Sequence; D001966:Bromine / Q000737:chemistry; D002462:Cell Membrane / Q000821:virology*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D014364:Tryptophan / Q000737:chemistry / Q000235:genetics; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D009698:Nucleoproteins; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus; D014364:Tryptophan; D001966:Bromine