Exploring the dimer-dimer association of the ebolavirus matrix protein VP40 at the human plasma membrane.

Abstract

Ebolavirus (EBOV) infections cause the deadly Ebola Virus Disease (EVD) which has a high fatality rate in both human and non-human primates. The EBOV genome codes for only seven proteins that can change structures and have multiple functions during the viral assembly. The matrix protein VP40 is the primary component that makes up the cylindrical structure of the Ebola virus. In addition to its other functions during the viral life cycle, it forms the virion's viral matrix layer below the lipid envelope. Once the VP40 dimers are trafficked to the plasma membrane (PM), they assemble into linear filaments which further associate to form the viral matrix. The end-to-end association of the dimers via their C-terminal interfaces is a crucial step during the formation of the matrix filaments. A crystal structure of the CTD-CTD assembly is available and it provides insight into the nature of the interfacial interactions. In this study, we investigated the lipid interactions of the dimer-dimer filament at the inner leaflet of the PM. We used all-atom molecular dynamics simulations of the dimer-dimer structure of the VP40 associated with the PM and identified the major amino acid residues involved in the lipid interactions. We also compared the differences in the lipid contacts of VP40 of a single dimer versus the lipid contacts with the dimer-dimer conformation.