Transcription
All right, so in this video, we're gonna talk about the third and fourth levels of protein folding. That's the tertiary and quaternary levels, and we're going to be using our model again. And so, uh, so far, we've done the primary level, which is the order of the beads. And we've done the secondary level, which is the the helices, the alpha helices and the beta sheets. So I'm just gonna roughly do that in my diagram. It kind of looks like a messy snake right now.
All right, so, um, what is the tertiary or the third level? So the third level of protein folding, we're going to take our protein that's currently folded like this, and we're going to fold it up some more. We're just going to kind of tangle it on itself until it looks like this. All right, so there is still coils in here, if you could see, and there is still pleated sheets in here, but there's also additional fold, and it's all kind of folded in on itself. And that is what happens at the third level of folding. And every single protein goes at least to this level. Many proteins go the next stage on, which is the fourth level, which we'll get to in a second. But some don't. Some just stay here. But everything goes at least to the third level. So what causes it to fold up into this giant big blob like this? Well, let's look at that on the next slide.
So I'm gonna, um, disappear myself here. And here we can see, um, uh, sort of a basic idea of our, um, our protein that has alpha helices and beta sheets, uh, and then it kind of folds up. So it all folds up into like this. This is what we call a ribbon diagram. We use these a lot to show proteins, um. So the ribbon is really, um, standing in for the, um, chain of beads, the the chain of amino acids. And the ribbon helps you to see the alpha helix. So like you can see an alpha helix here, see how it's coiled? You can see a bit of pleated sheet here. You can see some more alpha helix over here, you know, so you can see that. But then you can also see these other loops and wiggles and other stuff going on in there. So this ribbon diagram is showing a a blobbed up protein with a lot of tertiary folds holding it together.
All right, so let's move on. What holds it together? Well, this is where those R groups that we spent a lot of time talking about, whether they were hydrophilic or hydrophobic, this is where they come into play. So, um, R group interactions is what holds together the third level of folding. So once again, if you can imagine this purple, um, snake is actually the chain of beads, and then sticking off of each bead, each separate bead has its own side chain. All right, so they're not showing all the side chains. There's obviously going to be side chains here and here and here on every single bead on this chain. That is focusing in on some of them. And you can see here how the chain is kind of taking a U-turn so that the R group sticking off of this amino acid down here is interacting with the R group sticking off of this amino acid all the way up here. So these two amino acids, the amino acid A and amino acid Z, are not side by side. There's a whole bunch more amino acids in the chain between them. But when the whole thing folds up, it ends up with the R groups from this amino acid and the R group from this amino acid kind of lying side by side in three-dimensional space because of the fold that's happened. And you can see that the R groups are making an interaction here. Now, in this specific case, it's a our friend, the hydrogen bond, that we've seen many, many times before. Um, so the hydrogen bond will happen anytime you have partial charges on the R groups, which here we're going to have a partial positive on that H because it's attached to an O. And here we're going to have a partial negative on this O because O is always such a bully and wants all the height, all the electrons. So there's going to be a weak attraction between these two functional groups, which is going to hold this kind of fold in place.
Now, there are four main interactions that happen between R groups. So we're going to go through them all. The four types of interactions between R groups. So obviously, here's one of them, the hydrogen bond, when R groups have partial charges. I'm going to bring myself back here. I don't like being invisible. Hold on. Oh, there we go. I also don't like being that big. All right, so, um, R groups can have partial charges like this situation here on the left, and that can create an attraction. So a hydrogen bond, that's one thing that can happen. Some R groups are actually charged, like not just a partial positive, but a whole positive charge, like this, um, group down here, whole positive. And this one's got a whole negative. So when you have a whole positive and a whole negative attracting each other, you have a much stronger attraction, and that's an ionic bond. So some R groups can make ionic bonds between themselves, like like what's happening here. Some R groups can make hydrogen bonds between themselves, like what's happening over here.
Another thing that R groups can do, if they're hydrophobic, which is what we see here, is that they can interact together. We call this a hydrophobic interaction. What's really happening here is that this R group, which is attached to this amino acid, and this R group, which is attached to this amino acid, have found themselves in a very watery place, probably, which is basically what's it like inside your body. It's very watery. And those R groups are like, oh, we don't like the water. We're trying to stay away from it. And so they kind of get together, touch each other to try and push the water away, to protect each other from being having to touch the water. And that's what we call a hydrophobic interaction. Hydrophobic R groups will tend to try and cluster together to the inside of the protein to protect themselves from the water that's around the outside. So it's this is what we would call a hydrophobic interaction.
And then the last type of interaction that you have between R groups is this thing here called a disulfide bridge. And this is a kind of unique one. There is one amino acid that has a sulfhydryl R group, and it's called, um, cysteine. Sorry, it's not an S, it's cysteine. This is a special amino acid, not special, it's one of the 20, but it's the only one that has an R group that looks like this with a sulfhydryl group. So what's happened in this situation here is that this amino acid here is a cysteine in the chain, and this amino acid here is a cysteine in the chain. The chain's going on this way, and it's going on this way, but you happen to have a cysteine here. And the way it's folded up, the cysteine on this other side there end up being side by side. And when two cysteines get side by side of this and touch each other, their R groups interact. The two sulfhydryl groups can do a chemical reaction and create what's called a disulfide, two sulfur bridge, a disulfide bridge. You see there's a bridge connecting this side, this side to this side. Now, that's a very, that's very different to all the other interactions here. Hydrogen bonds can be easily broken, not very strong. It does have an impact, but it can be easily broken. An ionic bond can also be broken, especially if there's water floating around, this can get disrupted. They can just fall apart. Hydrophobic interaction, sure, there's nothing actually bonding these together, and then there's space between them, so they could be pried apart. But the disulfide bridge, this is a covalent bond. This is like a permanent linkage between these two S's, which kind of is like a staple kind of holding this fold in place. Um, so that's, that's the last kind of interaction, but it's also the most permanent. So we have hydrogen bonds, ionic bonds, hydrophobic interactions, and disulfide bridges. Four interactions, and they're all happening specifically between the R groups on the amino acids in the chain.
All right, so I'm gonna quickly flip back over and make myself large again. So heads up warning, um, let me see if I can make this work. There I go. All right, um, so if I was doing this on my model, right, um, you can see how the the beads are in in a certain order here. But if I was to fold them up, all right, like this, you can see how this pale purple one, this is really hard, this pale purple one is next to this dark, dark colored one here, right? They're not really next to each other in real life. They're separate on the on the chain. But when it folds up, they end up being side by side. So the R group on the purple one and the R group on the dark one could be doing a hydrogen bond between them, or they could be doing a disulfide bridge, or they could be doing an ionic bond, and that would hold this pleat in place. And that happens all the time. Any time you get two beads touching each other in this fold, even if they're not side by side in the chain, their R groups are going to be interacting.
One last thing I can tell you on this too. Let's imagine on this chain, uh, that all of the dark green ones, which it's hard for you to see, but I can see, if all of the dark green ones were hydrophobic, then they would all want to fold into the middle of my blob because they want to stay away from the water. So if I try and fold this so that all these green ones that I can see are, I'm putting all the green ones together and trying to put them in the middle, and then put all the rest of it like around the outside. So you can't really see the green ones. They're protected on the inside of this big blob, and the rest of it is all the way around the outside. All right, so that's, and so I make a specific shape, whatever shape it might be. It could be anything, whatever this protein is supposed to look like. Now, just imagine if there'd been an error when this was put together, and one of the beads that was that is supposed to be green and folded into the inside of the protein is actually the wrong bead was put there. And instead of a green one, they put a red one. And the red pro, the red beads love water. Then this bit here that's supposed to be tucked in to the protein ends up sticking out of the protein because it's got like a red bit that likes the water. Then I've changed the shape of my protein. And once you change the shape, it probably won't work anymore. It's like that messed up tool that won't function. And so that shows you why it's so important to get these beads in the right order. Because if you have them in the wrong order, or just substitute one, if it changes how the whole thing folds because of how these R groups interact to make this shape, then you're going to have the wrong shape. And if the shape is wrong, it won't work right. And you could end up with sickle cell anemia or cystic fibrosis or one of many nasty diseases, which is all down to bad protein folding. It's amazing. I'm gonna get into that later on. So that's tertiary or the third level of protein folding.