"If you can prevent the virus from making more RNA, then it can't replicate, which is a good strategy for developing antiviral medications," Bruhn said.
In X-ray crystallography, scientists manipulate a protein or some other molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can usually reconstruct the shape of the original moleculebut in this project, the challenge was interpreting the data.
Luckily, Bruhn attended a crystallography workshop in Chicago at the Argonne National Laboratory and there she met experts in the field and learned new techniques, such as ab-initio modeling, which leverages computational structure prediction. The team used a software pipeline called AMPLE developed by the Rutherford Appleton Lab and the University of Liverpool to generate models and finally determine the structure.
Echoes of Other Viruses
When the scientists solved the crystal structure of the P protein, they found that it forms a tetramer, with four proteins that join to form a single unit.
"It was surprising to us that this structure is so similar to those from measles and mumps viruses, even though they are only 5 to 26% identical in sequence," Bruhn said. "If two proteins have high sequence identity then you would expect that they would have similar 3D structures, but to see such similarity in proteins with such low identity was surprising."
She said this speaks to the importance of structural conservation over sequence conservation meaning that regardless of whether a protein has an identical sequence of amino acids or not, the structure could still be similar, especially when that structure has the important function of replicating the virus's R
|Contact: Mika Ono|
Scripps Research Institute