Bringing Structure to Biology
The image for August from our 2019 calendar features a recurring theme among the structures which inspire artists: the icosahedral virus. In this case, one which has the potential to devastate crop production worldwide.
Whether their host organism is a bacterium, a plant, an insect or a human, many viruses share a common solution to the problem of how to protect their (comparatively small) genomes in a way that can be encoded by that self same genome. Small genomes can only carry limited information, so building really large complicated proteins isn’t an option. The solution is to utilise symmetry, and construct a capsid (the ‘shell’ of a virus) out of many copies of simple building blocks, creating a shape known as the icosahedron. This is, essentially, a football (or soccer ball to our friends in the US). That symmetry makes the virus an attractive subject both to the artist and the structural biologist. The human eye considers symmetry to be beautiful and such geometric shapes are often used as the building blocks of artworks. For the structural biologist, symmetry can be put to work in increasing the signal-to-noise ratio of an experiment, helping define more precise structures.
While many viruses share the same overall shape, they differ greatly in the details of their structure, and it is that detail which can help us understand how they recognise the cells that they infect. The Plevka Lab at CEITEC study a range of viruses that can be devastating to the honey bee, a creature essential in pollinating many crops consumed by humans. The ‘Deformed wing virus’ tells you all you need to know of how symptoms of an infection with this virus present themselves.
Spiky footballs deform wings
The Deformed wing virus capsid is made up of three proteins, each present sixty times to generate the complete football-shaped shell. One of these proteins has an extra domain, only found in this family of viruses and which is folded in a unique way, not seen in any other protein. This domain, termed the P-domain, sticks out from the surface of the capsid. Plevka determined the structure of the virus by two different techniques, electron microscopy and X-ray crystallography. In these experiments the P-domain was found in a different orientation, suggesting it is able to sit in different positions on the surface of the virus. In the electron microscopy structure (PDB entry 5mv5), the P domain sits close to the five-fold symmetry axis of the icosahedron, forming ‘crowns’ on the surface. Using crystallography, however (PDB entry 5g52), the P-domain is much further from this axis, making the virus look like a spiky football.
Top: The overall structure of the P-domain show in in cartoons coloured from N-terminus (blue) to C-terminus (red). The putative catalytic triad residues are shown as ball-and-stick. Bottom. The X-ray structure of Deformed Wing Virus (left) and the cryo-EM structure (right). The P-domain is highlighted yellow in both cases.
Structures suggest targets for anti-virals
Intriginguely, the P-domain contains a motif of three amino acids commonly found in a family of enzymes which chop up (or hydrolyse) other molecules. It has an aspartate, histidine and serine arranged next to each other in a way similar to that seen that enzyme family. This suggests that the P-domain could be an enzyme, but whether it is active and contributes to the infectivity of the virus remains to be seen. If so, it is a potential target for anti-viral treatments.
The structure also revealed a second potential site for anti-virals. Inside the capsid, small portions of nucleic acid could be seen, hinting at how the viral genome packs within the virus. If this interaction between the capsid and the genome could be prevented, this may prevent new viruses from assembling, thereby preventing further spread of the virus.
About the artwork
Viral forms are are often similar to the Platonic solids that the ancient Greeks studied extensively. This image is a pen and watercolour sketch of the icosahedral viral capsid by Rebecca Sheng from Stephen Perse Foundation Sixth Form. The sketch was inspired by our fold-a-virus activity: why not try it for yourself!