Engineering a virus: Mutating protein sidechains alters capsid stability
Viruses are really interesting. We all know about them, mostly as those things that make us sick. In fact, only a very small percentage of viruses lead to illness in humans. This is a good thing, because there are lots and lots of viruses. I’ve been told that there are about 10,000,000 in a single milliliter of ocean water.
Viruses are, generally speaking, composed of two main parts. The capsid, or outer “skin” if you will, is made up of proteins. Inside of the capsid is the genetic material (this can be RNA or DNA). Scientists are interested in examining how these particles are constructed, both as a way to learn methods of combating viruses, as well as to attempt to “reverse engineer” them to do our evil bidding.
Today I came across a paper from the Proceedings of the National Academy of Sciences in which the authors (Carrasco et al) introduce a couple of mutations to the proteins in the model system of MVM (minute virus in mice) and examine the effects of these changes on the mechanical properties of the virus particle. Specifically, they shrink two of the amino acid sidechains known to be involved in hydrogen bonds with the DNA inside the capsid by mutation to Alanine. They found that this didn’t really change the overall appearance of the capsid.
What did change was the stiffness. The research showed that the alteration of these side chains made the virus particles weaker when they were prodded with a tip from an Atomic Force Microscope. The scientists also performed tests on capsids with no DNA, to show that the change in capsid stiffness was due to specifically to losses of these hydrogen bonds between the capsid proteins and the DNA inside.
It’s unclear whether this data has any direct clinical applicability, although the authors do point out:
that capsid residues involved in interactions with DNA patches, including N183 and D58 involved in the DNA-mediated stiffening effect, contribute to virion stability against thermal inactivation and to virus infectivity, which was reduced >10-fold by truncation of individual side chains interacting with the DNA
. The study does, however show that it is possible to manipulate the mechanical properties of these small biological macromolecules in a rational manner, and should lead the way to many more studies.
