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Proteins Unravelled

We hear about them all the time but have you really asked yourself: what exactly are proteins?

I want you to close your eyes and imagine a protein. Anyone with aphantasia gets a free pass on this exercise, but I suspect that most people still won’t be able to do it. The word “protein” is commonly used: we know we have to eat it, we know our muscles need it. But what does it look like?

Imagine you are threading together pearls on a string to make a necklace. You have at your disposal twenty or so types of pearls, each with a unique colour and slightly different shape. This string of pearls is a good visual analogy for a protein. Pearls are the building blocks of a pearl necklace and amino acids are the building blocks of a protein. They are bound to each other and form a chain. Now proteins don’t typically exist as shapeless strings of amino acids. Many bend, flip into accordion-like structures, and develop three-dimensional pits called pockets. These important contortions happen because different “pearls” in the protein have different properties: some attract water and some repulse it, some have an affinity for “blue pearls” and want to be close to them. Just like a few magnetized pearls in a necklace held in the palm of your hand will create areas of repulsion that will shape the object, specific amino acids do the same to the protein chain, often forcing the water-repulsing stretches inside the protein.This process by which a protein chain finds its most stable structure can often be helped by other proteins known as chaperones.

The final shape of a protein is essential to its function. You can imagine that long string of pearls twisted into the form of a glass, of a mat, of a lasso. And that’s the power of proteins: building blocks get strung together in a different order and create functional shapes. Each one of our cells has, by some scientific estimates, two thousand to one hundred thousand millions of these proteins in total, playing roles defined by their shapes and sequences. A protein like collagen, with its long bundle-like profile, acts like a cable in our connective tissue. Hemoglobin, another protein, uses its doughnut-like shape to accommodate oxygen and transport this precious molecule in our blood. A protein like DNA helicase functions as a wheel to disentangle the double helix of our DNA (like unbraiding hair) so that copies can be made of it. Then there is the invaluable service that proteins provide in signalling. When information about something happening outside a cell needs to be conveyed to the inside of that cell, certain proteins act like the signal fires in the lighting of the beacons sequence in The Lord of the Rings. One protein receives a molecular torch (a phosphate group), which activates it to give a similar torch to another protein, and this signal exchange cascades down into the cell to eventually influence the production of more proteins. Outside of cells, smaller protein-like molecules like insulin act as hormones, secreted by an organ and sent throughout the body to help regulate vital functions.

Given their importance, you may wonder where proteins come from. Proteins are made in little factories inside our cell and the order in which each “pearl” (or amino acid) is added to them is encoded in our DNA. That is the main function of a gene: a piece of DNA that tells the factory how to assemble a specific protein. Each stretch of three DNA letters inside a gene corresponds to a particular amino acid, so the molecular factory reads these letters three at a time and plucks the right amino acid to add it to the chain. Some of these amino acids are created by our own body, while essential amino acids must come from our diet.

We get our amino acids from any food that contains proteins, like meat, pumpkin seeds, dairy products, tofu, nuts and beans. Our protein intake is dictated by our age and specific needs: Dietitians of Canada recommend about 0.8 gram of protein per kilogram of body weight for most adults over the age of 19. This means that an adult who weighs 80 kilograms (or 176 pounds) would need on average about 64 grams of protein each day. These ingested proteins get broken down into amino acids inside our digestive system. Many of them will be made available to cells for the purpose of assembling new proteins, while others get rerouted to other pathways in our body’s metabolism. And proteins don’t last forever: our body breaks them down and recycles their individual “pearls.” So couldn’t we simply live off of our current supply of proteins, recycling their building blocks forever? The answer is that we lose some of these building blocks in our hair, our skin cells, our urine and the cells lining our gastrointestinal tract, and some amino acids are even turned into glucose for energy and into other molecules our body needs, so our stocks have to be replenished.

As lovely as proteins are to our existence, some are not above causing us harm. The protein ricin, made by the castor bean, is a toxin which targets the very molecular machinery in our cells that makes new proteins. Its effect on the body is devastating: starting with vomiting, abdominal pain and diarrhea, the toxicity triggers hypovolemic shock (a result of massive fluid loss) and multiorgan failure. Many toxins secreted by animals such as spiders are mixtures of smaller proteins called “peptides.” These toxic peptides can interfere with the exchange of electrically charged molecules inside and outside our cells, like calcium and potassium. Proteins naturally found inside our own body can also be tied to disease. In Alzheimer’s disease, specific peptides and proteins appear to contribute to the condition by being made in too large of a quantity and/or by not being cleared from the cells quickly enough, leading to an accumulation. More broadly, genetic conditions like Huntington’s disease, sickle cell anemia, and muscular dystrophies arise because a mutation in the genetic blueprint ends up creating an abnormal protein that can’t function correctly.

In this COVID era, I’d be remiss if I didn’t point out the obvious link between proteins and the coronavirus. Those spikes at the surface of the virus that give those infectious particles their crown-like appearance and that help the virus attach itself to our cells? They are glycoproteins, meaning proteins onto which a sugar is attached.

Finally, proteins are like babies: they need names. Some scientists take the descriptive route: there’s a protein called “platelet-derived growth factor” because it is a growth factor derived from blood platelets. Others fancy a more clever name: “Methuselah-like proteins” are named after the Biblical figure known for his longevity and are linked to aging in insects. But some scientists just want to have fun. A Japanese scientist in 2008 discovered a new protein in the eye. He must have been a fan of anime because he named it “pikachurin.”

Take-home message:
- Proteins are strings of amino acids that fulfill a function and can be thought of as pearl necklaces twisted into specific shapes
- Many simple genetic conditions are due to an error in the DNA which creates an abnormal protein that cannot function properly


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