Understanding the Activated Form of a Class-I Fusion Protein: Modeling the Interaction of the Ebola Virus Glycoprotein 2 with a Lipid Bilayer

Abstract

Fusion of the viral and target cell membranes is a key step in the life cycle of all enveloped viruses. Here, a range of structural data is used to generate an evidence-based model of the active conformation of an archetypical type-I fusion protein, the Ebola glycoprotein 2 (GP2). The stability of the trimeric complex is demonstrated using molecular dynamics and validated by simulating the interaction of the complex with a lipid bilayer. In this model the fusion peptides project away from the central helix bundle parallel to the target membrane. This maximizes contact with the host membrane, enhances lateral stability and would explain why, when activated, viral fusion proteins are trimeric.