Posted by 
Researchers were able to mutate Viral Protein 40 (VP40) changed the residues of the protein, blocking the budding and replication of Ebola virus in a model system. VP40 is a peripheral membrane protein that regulates viral budding from the plasma membrane. It interacts with a human plasma-membrane lipid, phosphatidylserine, to facilitate replication of the virus. Animal viruses cross membranes before entering and exiting the cell.
The research team, led by Robert Stahelin of Purdue University, found the specific parts of VP40 that bind with the lipid: a cationic patch on the end of an amino acid chain. This site controls the ability of the protein to form a lipid layer that protects the virus from the outside environment. Water-attracting residues at this site are critical for membrane penetration and budding. Substituting those residues with alanine, which is hydrophobic, reduced lipid binding by 40-fold and stopped localization to the plasma membrane.
VP40 is a transformer protein, it can rearrange itself into different structures like monomer, dimer and octamer. These structures interact with the lipid differently. The dimer is best equipped to facilitate replication, performing twice as well as the monomer, and nearly 10 times better than the octamer.
Different oligomeric structures bind differently with the human lipid cells, knowing how and where the protein interacts with the lipid could allow researchers to target Ebola with therapeutics. This how the virus uses human cell membranes to replicate and form new virus particles. The virus needs this one lipid to form the new particle and infect other cells. Cellular and in vitro models were used in the study. In vitro models were used to quantify how VP40 binds to synthetic membranes.
The researchers mutated the DNA code to change the amino acid sequence of VP40, purified the proteins to homogeneity and compared their bindings to VP40. In cellular experiments, live cell imaging was used to monitor VP40 localization in human cells. The movement of the mutant VP40 and the original VP40 were compared to see how they bind to the human cell plasma membrane, the site of viral replication.
haleplushearty.org