According to the study, the researchers making possible by an array of different structural and molecular biology techniques, with the structural component being carried out at Diamond Light Source. The team used three different techniques, Cryo-EM; crystallography and SAXS which are powerful when using on their own; but even more so in combination when addressing complex, structural biology.
But the arrangement of atoms within a protein; that the human flu virus uses to make new copies of its genetic information. Without this multifunctional protein; known as a polymerase, the flu virus cannot survive. A key finding of the study is that the polymerase can exist in two forms, a monomer and a dimer. It is only when the polymerase dimerises that specific functions are switching on.
The research team saw the dimeric form of the polymerase was formed by a specific region of protein and when the region was disrupted, the polymerase couldn’t work. This finding presents a brand-new way of potentially inhibiting the flu virus which means we could develop new drugs and flu treatments in the future. Structural biology has been using to understand important human diseases for decades.
Techniques for virus protein
By understanding cellular interactions on a molecular level, it is possible to find treatments and cures. However, we lack a lot of structural information for many functionally important proteins. Influenza A viruses are the most common cause of seasonal flu in humans and cause annual epidemics around the world and occasional pandemics, representing significant public health and economic burdens.
Influenza A virus is an avian virus, which is able to jump species, infecting both humans and other animals. When influenza virus infects a host cell, it starts to make many copies of itself as the disease spreads. The protein that drives this copying is the viral RNA polymerase which replicates the viral RNA genome and makes RNA templates for protein synthesis. In order to understand how the polymerase works in mechanistic detail you need to work out the structure of the RNA polymerase in atomic detail.
As the study describe a high resolution structure of the RNA polymerase in multiple conformations which showing; how the protein is able to replicate the influenza virus RNA genome. They observing that the protein could either form monomers or dimers. The crystal structures of the dimerised polymerase clearly showing; the region of the protein that formed the interface holding the dimer together.
The research team wanted to know if this region was important to maintaining the dimer and more importantly; if they could disrupt the activity of the polymerase by forcing it into a monomeric form. They mutated various parts of the dimer interface to produce a selection of mutant proteins that could not form dimers.