Proteins that belong to a recently identified class “Transformer proteins” show a remarkable ability to rearrange their structure to significantly different conformations that perform completely different functions. One such protein is the Ebola virus protein VP40, which exists in different conformations depending on the required function: a butterfly shaped dimer is involved in the transport of the protein to a membrane, a hexamer to form the viral matrix, and an octamer ring structure to bind to RNA and regulate viral transcription. The viral matrix layer underneath the lipid envelope of Filoviruses is formed by the matrix protein VP40, and provides shape and stability to the virus.
Theoretical and Computational Biophysics led by BSI members Bernard Gerstman and Prem Chapagain, along with recent Worlds Ahead Graduate, Jeevan GC, in collaboration with experimentalist Professor Robert Stahelin at the University of Notre Dame, has been investigating how VP40 is associated with, and localized at the lower leaflet of the plasma membrane. These investigations may prove useful not only for the basic understanding of the viral flexibility and assembly but also in determining pharmacological strategies targeting VP40 to inhibit viral budding.
- Bhattarai, N., GC, J.B., Gerstman, B.S., Stahelin, R.V, Chapagain, P.P. (2017). Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer. RSC Advances, 37(7) 22741-22748
- GC, J.B., Johnson, K.A., Husby, M.L., Frick, C.T., Gerstman, B.S., Stahelin, R.V, Chapagain, P.P. (2016). Interdomain salt-bridges in the Ebola virus protein VP40 and their role in domain association and plasma membrane localization. Protein Sci, doi:10.1002/pro.2969
- GC, J.B., Gerstman, B.S., Stahelin, R.V., Chapagain, P.P. (2016). The Ebola virus protein VP40 hexamer enhances the clustering of PI(4,5)P2 lipids in the plasma membrane. Phys Chem Chem Phys, 18(41):28409-28417