title: Pre-transmembrane sequence of Ebola glycoprotein. Interfacial hydrophobicity distribution and interaction with membranes.
abstract: The membrane-interacting domain that precedes the transmembrane anchor of Ebola glycoprotein has been characterized. This aromatic-rich region is predicted to bind the membrane interface adopting an alpha-helical structure. Peptides representing either the Ebola glycoprotein pre-transmembrane sequence, or a 'scrambled' control with a different hydrophobic-at-interface moment, have been studied. Insertion into lipid monolayers, changes in intrinsic fluorescence and in infrared spectra demonstrated that only the wild-type peptide bound the interface under equilibrium conditions and adopted an alpha-helical conformation. The presence of the raft-associated lipid sphingomyelin did not affect membrane insertion, but it stimulated highly the membrane-destabilizing capacity of the pre-transmembrane sequence. A parallel study of the effects of the viral sequence and of melittin suggests that Ebola glycoprotein pre-transmembrane sequence might target membranes inherently prone to destabilization by lytic peptides.
authors.affiliation: Unidad de Biofísica (CSIC-UPV/EHU) and Departamento de Bioquímica, Universidad del País Vasco, Aptdo. 644, 48080, Bilbao, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: Sáez-Cirión
authors.forename: María J
authors.initials: MJ
authors.lastname: Gómara
authors.forename: Aitziber
authors.initials: A
authors.lastname: Agirre
authors.forename: José L
authors.initials: JL
authors.lastname: Nieva
mesh_terms: D000595:Amino Acid Sequence; D029043:Ebolavirus / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013109:Sphingomyelins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D013109:Sphingomyelins; D014763:Viral Matrix Proteins; C110614:transmembrane glycoprotein, Ebola virus