Pre‐transmembrane sequence of Ebola glycoprotein

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 α‐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 α‐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.