Viral Fusion Peptides Incorporated in Monoolein Membranes: Secondary Structure and Lipid Phase Behavior

Abstract

The viral membrane fusion is mediated by fusion proteins located on the virion surface. The process involves major changes of the membrane curvatures leading to non-bilayer structures. For a better understanding of the way fusion proteins steer this process, we have studied the interaction of two different hydrophobic segments, HA2-FP and TBEV-FP, which are known as “fusion peptides”, with monoolein mesophases as a function of temperature and pressure at limited hydration. The fusion peptides are derived from the influenza virus hemagglutinin fusion protein (HA2-FP) and from the tick-borne encephalitis virus envelope glycoprotein E (TBEV-FP). The changes of the monoolein phase behavior upon binding the peptides have been determined by X-ray diffraction. FTIR spectroscopy has been used to analyze the concomitant secondary structures of the peptides. We have found that the interaction of the fusion peptides with monoolein as well as the change of the temperature and pressure dependent lipid phase behavior differs markedly depending on the fusion peptide. However, they both destabilize the fluid lamellar phase and favor phases with negative curvature, i.e. inverse bicontinuous cubic and inverse hexagonal phases. We could show a partial reversion of these peptide-induced phase changes by the application of high pressure, demonstrating that a less dense packing of the monoolein membranes achieved by the fusion peptides promotes the negative curvature of the membrane. Interestingly, the secondary structures of the fusion peptides appear unaffected by monoolein fluid−fluid phase transitions, suggesting that the fusion peptides are the structure dominant species in the fusion process of lipid membranes.