Memrane binding induced conformational changes in Marburg virus protein VP40 dimer

Marburg and Ebola viruses belong to the Filoviridae family and their infection causes hemorrhagic fever.The Marburg virus is a lipid enveloped virus and its viral matrix is formed by the matrix protein VP40. As in the Ebola VP40 (eVP40) dimer, the crystal structure of the Marburg VP40 (mVP40) dimer contains residues that form a basic patch at the membrane interface. However, compared to eVP40, the basic patch of mVP40 is significantly broader, suggesting differences between the dimers in plasma membrane (PM) localization. Using molecular dynamics simulations, we investigated the VP40 dimer interactions and the roles of various residues and lipid types in PM association as well as conformational changes. Despite the significant structural differences, mVP40 is found to adopt a configuration similar to eVP40 after associating with the membrane by reorienting the monomers in the dimer. We compared the structures of the mVP40 dimer in both lipid and lipid-free environments and found that the lipid interaction is needed for the observed conformational reorientation. Such conformational changes may be important for the mVP40 dimer to stabilize at the membrane surface and ensuring virus-like particle formation and budding from the plasma membrane.