Structural biology has been used to understand important human diseases for decades. 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 virus is an avian virus, which is able to jump species, infecting both humans and other animals. 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. 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.

The reason that no structures existed for this protein until recently is that it was very difficult to produce in a highly purified form. In order to do structural studies, proteins normally have to be cloned and produced in large quantities in bacteria, and sometimes it’s just not possible. However, several years ago, the groups of Ervin Fodor and Jonathan Grimes, along with others around the world, discovered a way to produce the flu polymerase in large amounts. Then the race was on to determine the structure.

Fast forward to today and the team has published the structure in the journal Nature. In the article they describe a high-resolution structure of the RNA polymerase in multiple conformations which shows how the protein is able to replicate the influenza virus RNA genome. They observed that the protein could either form monomers or dimers. Grimes explained: