The twilight world between chemistry and life

Viruses live in a twilight zone, somewhere between life and its ingredients. My fifth structure of Christmas emerges from that zone to wreak havoc on cattle: the foot-and-mouth-disease virus.

Consider the virus: a beautifully crafted set of molecules perfectly arranged to do one thing, and one thing only: subvert life forms to make more of itself. But what is it? Is it ‘alive’, in the conventional sense?

Viruses cannot do anything without their host cells. On their own, they are as inert as rock or charcoal. But if they drift into the right sort of cells, they spring to ‘life’ and set about their mission of hijacking that cell’s machinery to make more viral proteins.

There are millions of viruses on the planet, parasitising just about every type of cell: bacterial, animal, plant, you name it. Indeed, there are some viruses that infect other viruses.

‘Life’ and ‘art’

Viruses exist in one of two general states, which you could think of as their ‘life’ cycle. In one state they are drifting around, either in solution or in the air, mainly just hanging around and ‘hoping’ to bump into the right sort of cell. There is a transition point, when the virus collides with the ‘right’ sort of cell. Then there is the active state: once it has made contact with a cell, the virus focuses on getting into it, taking over the ribosome and making more of itself.

The outside of the virus – its protein coat – protects the virus while it’s drifting about and while it’s working on breaking into the cell’s membrane.

The combination of a virus’s tiny size and the simplicity of its task often gives rise to astonishingly beautiful geometric shapes. If they weren’t so awful biologically, one could simply admire them as a sublime collection of geometrical Greek objets d’art.

Crystallising the coat

Viruses might be considered only half alive, but they form some of the biggest structures determined by X-crystallography.

The regular structure of a virus’s coat makes it easy to crystallise (although sometimes one can only crystallise part of it) but these structures are huge and often structural biologists make use of internal repetition to improve the understanding.

When proteins crystallise, they form a repetitive structure across the crystal volume, for example a bunch of cubes stacked on top of each other. There are many different ways to make the repeating pattern of a crystal, which are called space groups. In a rather glorious meeting of maths and the physical world, there are precisely 65 crystallographic space groups available to proteins, enumerated by 19th Century mathematicians before the advent of X-ray crystallography.

All crystals fall into one specific space group, which defines the repeated unit (e.g. cube) and the way it packs to form the crystal. But that repeat unit (called the “asymmetric unit”) may or may not be the actual biological bit. Indeed, sometimes the ‘right’ biologically relevant unit is made up of several asymmetric units.

In the case of virus particles, the large asymmetric unit often has many internally repetitive components. In this case, the Foot and Mouth virus has a five-fold internal symmetry to parts of its coat – something which is impossible to achieve in a crystal (five fold symmetry is not an allowed crystallographic space group), but scientists can make the assumption that the repeated structure is the same across all these biological units. This internal repetition can be leveraged to get better resolution on the internal structure of each component. That allows us to explore and understand this type of molecular life in remarkable, atomic detail.

Foot and mouth disease

The foot-and-mouth-disease virus is a large RNA virus that causes a horrible, highly infectious disease in cattle. It has a shell (called a ‘capsid’, which is made of protein) that contains a single strand of RNA and binds to a receptor site on the membrane of a host cell. It’s kind of like using a magnetic ID card to open a door. Once it’s inside, the capsid dissolves and the RNA takes over the cell’s ribosomes to get itself translated into more viral proteins.

The kicker is that some of these proteins block the synthesis of normal cell proteins. So the cell is completely taken over. It becomes good for nothing but making virus – until it eventually bursts.

It’s a nasty little thing.

A well-oiled subversion machine

A virus is a massive information complex, with everything packaged up just so. The virus stores its information either as DNA or as RNA. When it uses RNA it is better placed to subvert a host cell’s RNA-making machinery, which might be why RNA is more common. Another reason we might see more RNA viruses is that these half-life forms have been around since the dawn of life, and the first life forms to emerge were based on RNA.

Whatever the reason the geometric, pared-down and utterly focused nature of viruses is fascinating – beautiful in form but horrible in action.

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