Team:UCopenhagen/TestNina
Proteins: Tiny Biological Machines
Written by Victoria Rasmussen, BSc student in Molecular Biomedicine
Proteins are one of those science-y things that people like to talk about. They are sometimes called the “building blocks of life”by myself and people way smarter than me. That is a bit of an abstraction that in my opinion does more to confuse than to educate. Proteins aren’t magic, they are very real things.
Life and everything that sustains it is unfathomably complicated and this means that scientific communicators often takes shortcuts to get their points across. I believe this is where the “building blocks of life” phrase coms in to the picture. The description does its job in explaining how important proteins are for life, but that’s about all it accomplishes. So here I’m going to try and explain how proteins work, and I promise it isn’t magic. The scientific community’s understanding of proteins has progressed so far that synthetic man-made proteins are being made right now! We know enough to be able to design these things, but we still feed the public that — in my opinion — unfulfilling explanation.
Removing the mysticism from proteins involves digging into some science, and that means that the explanation runs the risk of being super boring, here’s wikipedia’s version of an introduction to proteins:
"Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues.”
Wow, super interesting! Even for me, sitting alone in a café sipping the last of my unsweetened ice tea, that was an unsatisfying read (almost as much as this ice tea, do not recommend). Of course wikipedia is not normally a place we go to for exciting info, and the overall article was quite good as far as scientific content goes! But it’s not much of a hook for people interested in science who don’t have any prior experience. As a budding — very much budding, so please keep this in mind when you read further — scientist who has an interest in communication all I see when searching for resources is a giant canyon separating superficial magic-sounding non-explanations from hardcore scientific info. There’s nothing in the middle! In my perfect world there is information on every single level, enough to sate everyone’s curiosity and enough to maybe ignite the science-passion in more people.
With that rant over with, let me introduce you to the stars of the evening: PROTEINS!
Proteins are pretty much everywhere. They make up the food you eat and the medicine you take, insulin that keeps diabetes under control and the steak you had for dinner not long ago, your dog and your body and the bacteria and vira that makes you sick. All of it contains protein. In my other article I talked about the bacterial injectisome, which is also made from proteins. I mentioned the toxins and things that got injected from the bacteria, through the injectisome and into the living cells, which is also-yes you guessed it- protein.(If you missed my article, click here)
So, I think you get the picture. Proteins are pretty damn important. They can be good or bad for us humans, but here’s the one unifying thing all of them have in common: They all have a function. Some make our muscles move, some cleave food into pieces so tiny they can be absorbed through our intestinal surface and others control our blood sugar/fat/hormone/you-name-it levels. Others makes our cells stop working properly and really mess with our bodies. The functions of proteins are very very diverse — Very much like the machines we use. A coffee maker and a car look different, but in the end they are both exactly that: Machines! It’s the same way with proteins.
A coffee maker needs to look a certain way and have a certain set of components. It needs to be able to plug into something to get electricity and it needs something to load the coffee beans. The coffee maker has been perfected to do one thing, make coffee. Proteins also need specific parts to let it do its own thing. Function follows form. The structure and look of a protein dictates what it is able to do. If we want our protein to be able to, say, recognize another thing, we want those two to be able to interact. This can happen in lot of different ways, but let’s start with magnets. I’m sure you know that negative and positive charges attract. The red and blue poles want to stick together and, as part of this, positive and positive/negative and negative push each other apart. This isn’t only a thing for magnets, but for everything! By having a negative charge on one protein and a positive charge on the other you have created a so-called interaction site. They will attract and bind each other in the same way a pair of magnets will — they’re now sticking together.
Figure 1: Cartoon representation of a protein interaction by Eric Francisko
This is all well and good, but what are proteins made out of? How do they work? This is a very good question. Proteins are, like Wikipedia said, made out of amino acids. These are teeny tiny molecules that can stick together in a long chain. Together these amino acids make our protein. Imagine a massive chain made out of identical links. The identical links are the amino acids, but one single short side chain sticks out from those links — like a different charm hanging on each chain link in a charm bracelet. We call the identical part of the protein the backbone, and from the backbone hang the charms, which have different properties. Some of them can have an electric charge, meaning they attract the opposite charge. Some want to bind to a specific atom. Some are hydrophobic, which means they are afraid of water! These particular groups hate anything water-friendly, they only want to hang out with other hydrophobic groups.
An example you can try at home is throwing a bit of oil in a glass of water. The hydrophobic oil molecules will stick together and try to minimize their interaction with the water! Hydrophobic amino acids will bind as part of the backbone, because they are still amino acids after all and are therefore part of the chain, but their water-hating sidechain will do everything in its power not to be close to water. It will seek out other hydrophobic groups and bind to those instead. Like most people, amino acids have a type! And some are more promiscuous than others.
So from a backbone there will be several free side chains that are ready to react and bind to other groups. These could be free groups on itself or those on another protein. Keep in mind that these groups are still stuck to the backbone, but this will not deter them from finding a type-fitting partner! They will drag their backbone with them when they find that specific perfect group they can bind to. Imagine the long chain being bent and dragged all over the place as its side-chains are searching, finding and binding to their perfect matches. It will not be linear after everything is said and done, no, it will have been forced into a shape!
Imagine that coffee maker again, it is made out of metal and plastic (I assume, I’m not a coffee maker scientist unfortunately). That metal and plastic is then held into place by screws and glue and all kinds of good stuff. If we remove those things that make it keep its shape, then the coffee maker breaks. It can no longer make coffee. For our biological machines that same thing is happening! But this time the screws and glue are these side groups that want to stick together. Their interactions are making our backbone take the shape it needs to do its thing! Our protein is no longer a linear shapeless thing, but a machine! With parts and form and function! And by changing the amino acids’ sidechains you can change the proteins’ function. Just like you can make other machines than a coffee maker using metal and plastic if you put it together differently.
Now I want to put our protein knowledge to the test. And talk more about the injectisome, cause it’s super cool. I mentioned the needle-like system that penetrated the cell membrane and then sent a bunch of toxic and cell behaviour-changing proteins through and into the living cell. This is not a great thing for us and our health, and I think we can safely classify a lot of these injected proteins as bad. Now the injectisome is actually made out of protein. But — It’s not sharp or anything, so it doesn’t penetrate the cell barrier by cutting with something sharp. What the bacteria actually does is it makes a so-called tip-protein. This is a hollow protein that contains a bunch of hydrophobic amino acids. These amino acids are in contact with water, which they absolutely hate! The tip-protein is now very uncomfortable surrounded by water and it is searching desperately for something hydrophobic it can bind to in order to hide. Imagine that it encounters a cell barrier, for they too are hydrophobic. Membranes are actually made out of oil and fat, which are exactly what our hydrophobic amino acids love to interact with. What happens now is that this tip-protein will be dragged away from the gross water surrounding it by its hydrophobic amino acids and sets itself into the oily hydrophobic membrane. Now with this hollow tip-protein inserted into the membrane, the rest of the injectisome can dock here and inject proteins through the hole! (Source)
This interaction between the tip-protein and the cell membrane is only one example of a protein with a very specific function. In this case it is all about creating the hole in the cell membrane that the EHEC bacteria uses to send toxins through.
Proteins are tiny biological machines built with a purpose made possible by its form. Some are good for humans, others are bad. Most- if not all- can be highjacked and used for other human-dictated purposes. This is what synthetic biology is all about! And why a better understanding of proteins is important for everyone.