 Welcome back everybody. This is an extension of the previous video. The previous video we ended by talking about how different protein molecules have a specific sequence, their own special order of connecting the amino acids to each other in, and the order that you connect them in or the sequence that they're connected in controls what type of job the protein molecule does. This little bit is new, and we haven't discussed it in the previous video. The sequence that you connect the amino acids to each other in actually makes protein molecules fold up in 3D in their own special way. Now, I can't really draw anything in 3D because I'm horrible at drawing, but if you didn't know any better, I'm going to pretend that each amino acid is like a little ball connected to each other in a protein molecule. So here's amino acid number one, a little ball connected to amino acid number two, and let's say that there's a hundred of them, right, number three, it goes on and on, and here's number 99, and there's number 100. If you didn't know any better, the way that we've been talking about a bunch of amino acids connected to each other, you might think that the molecule that you make is just like this big long string, right, if there's a hundred little balls connected to each other, maybe it's just this big sort of long molecule like that. In reality, what happens is the order that you connect the amino acids in makes every protein molecule fold up in 3D in its own special way. So even though I have a hundred amino acids and you might think that they're like this, what ends up happening in real life when the protein molecule gets made is it might fold up in its own special way. So this is my horrible way of showing you the protein molecule folded up properly. One of the other pieces of information that I want you to know is that every different type of protein molecule folds up in 3D in its own special way. So one protein molecule might fold up like this, another protein molecule might fold up like that. Again, these are just cartoons, they obviously don't fold up like that, but you get the point hopefully. The way that the protein molecule folds up helps control what kind of job it does. And I'm going to show you a video on YouTube that shows you a protein folding up. So in this particular video, again this is just a cartoon, it's very difficult to see real protein molecules fold up, but you'll get the idea here. What they're going to show you is one particular protein molecule. At the beginning I think they're going to show you every single atom in the molecule, but then that's really complicated, so they are going to replace that I believe with the one-letter abbreviation for all of the amino acids connected to each other, and then even that's a little bit complicated and they're going to replace every one-letter abbreviation with just a little ball, and each little ball is supposed to be one amino acid connected to the other ones. And at the beginning, the protein molecule is going to be unfolded, and you're going to see it gradually fold up in its own 3D way. Here we go. This is the name of the protein molecule, you do not need to know this. Here's the protein molecule, all of the atoms, there's the one-letter abbreviation. This is the protein molecule with each little amino acid is like a little ball, it is not folded up, and here it is in the process of folding up, it's still not quite folded up, and now it's folded up. It looks like there are little spaces between there, but you'll see that it doesn't, there are not really empty spaces there, it's pretty tightly packed once they show you everything filled in. So there it is filled in, whatever that protein is, there it is properly folded up in 3D. So every protein molecule folds up in its own special way in 3D. This is the three-dimensional shape of one specific protein molecule called kinesin. Kinesin is a molecule in all of our cells whose job is to carry other molecules around to different parts of the cell. But you can see that chemists and biologists probably spent years trying to figure out the three-dimensional shape of this specific molecule. It is not an easy thing to do, there are reasons for wanting to do this. A lot of times people feel like if they can figure out the shape of a molecule, it can help them understand what job it does and how it does its job. Again, I don't want you to get lost in the details, but there are some things, right? There's an N and a C here, you probably know what those mean. This is one end where the amino acids start getting connected to each other. This is the other end. But for this particular molecule, when it's folded up properly, the N-terminus and the C-terminus end up being close to each other. And there are all sorts of weird little shapes, right? There's this spiral here, there are all these spirals, there are other things. This is just to show you an example of how complicated the 3D shape can be for a protein molecule. That's all I want you to know here. These bullet points I also want you to know as well, but I don't want you to get lost in the details of this picture. This is very important. If a protein molecule doesn't fold up properly, it will not do its job. And unfolded proteins, so proteins that are not folded up properly, not doing their job, can be a big problem for living things, for ourselves. This is a little bit of new information. If you remember a couple of videos back, I said that there are 20 amino acids and you can break the amino acids into two categories. The amino acids that are hydrophobic, that means there are some amino acids that don't like to mix with water, and there are also amino acids that are hydrophilic. Those are amino acids that do like to mix with water. Well, there are some general rules about these kinds of amino acids. The amino acids that are hydrophobic, as a rule, they tend to be buried on the inside of protein molecules. So I just spent 10 minutes talking about how protein molecules like to fold up, right? So I'm going to pretend to fold it up for protein molecule. Well, if this molecule is bouncing around in your cell, that molecule is mostly surrounded by water molecules. But some of the amino acids in this molecule don't like to mix with water. They are the hydrophobic amino acids. And as a rule, they tend to be buried on the inside of the protein molecules, away from the water. And the hydrophilic amino acids tend to be on the surface of protein molecules. So if here's my properly folded up protein molecule, and it's mostly surrounded by water molecules, well, this protein molecule also has hydrophilic amino acids as well. And the hydrophilic ones are usually on the surface, because they're pretty happy interacting with the water molecules. So this is a general rule that I want you to know. Hydrophobic amino acids are usually on the inside of a protein molecule. Hydrophilic amino acids are usually on the surface. There are many exceptions to this, but this is generally true. So just to drive this point home, remember these amino acids are hydrophobic because it says so right there. As a rule, you will find these amino acids buried on the interior of protein molecules once they fold it up. And as a rule, all of the other ones, hydrophilic, these ones, and these ones as well, these you usually find on the surface of protein molecules. So what does this have to do with the price of bananas, right? Who cares? Well, it turns out that a lot of human diseases are related to protein molecules folding up properly or not folding up properly. One example of this is sickle cell disease. If you are familiar with sickle cell disease, everything that I say is going to be old news to you if you're not. This is a picture of red blood cells from a person who has sickle cell disease. People with healthy red blood cells make red blood cells that look like this or like this. They look like round fluffy pillows. People who have sickle cell disease, they might make some healthy red blood cells, but they also make red blood cells that have these weird shapes. They're kind of long and pointy. The problem with red blood cells that are long and pointy like that is they get stuck in narrow blood vessels and they can clog those blood vessels. And if they clog the blood vessels, they cause a tremendous amount of pain. So sometimes these kind of stretched out red blood cells get stuck in narrow blood vessels. When this happens, people have difficulty breathing. There's a tremendous amount of pain. They get significant tissue damage. People who have sickle cell disease have average life expectancy that's a lot less than someone than a healthy person who does not have sickle cell disease. So what does this have to do with protein molecules? Well, first thing I want you to know is that red blood cells, you should think of them as bags of hemoglobin. What I mean by that is a large part of what the red blood cells do is they carry hemoglobin protein molecules to your lungs. The hemoglobin protein molecules pick up oxygen from your lungs, and then the red blood cells leave your lungs and they go to other tissues and then the hemoglobin molecules release the oxygen to the other tissues that need it. So these red blood cells are basically filled with a whole bunch of hemoglobin protein molecules. If you look at people who are healthy, well, people who do not have sickle cell disease, if you look at the sequence of the amino acids in hemoglobin, they have an E. E is the one letter abbreviation I believe for glutamic acid. So they have, I think this is, they have a leucine amino acid connected to a threonine amino acid connected to proline and glutamic acid and glutamic acid, et cetera, et cetera. This is for people who do not have sickle cell disease. This is part of the hemoglobin protein molecule. People who have sickle cell disease in the most common version of sickle cell disease, the people who have the disease, they make almost the same kind of hemoglobin protein molecule except instead of this E, which is, stands for glutamic acid, their bodies put another amino acid in called valine. Now at this point I'd like you to pause the video and look at your book or whatever you have and figure out whether glutamic acid and valine are hydrophobic or hydrophilic and then you can on pause the video and we will talk. If you unpause the video, what you'll notice is that glutamic acid is hydrophilic. That means this amino acid likes to mix with water. Problem is valine is not, valine is hydrophobic. So what happens in people, well, what happens in people who are healthy, people who do not have sickle cell disease, they make hemoglobin molecules that fold up properly, pretend this is a bunch of hemoglobin molecules pulled it up properly and this E here is hydrophilic. It likes to mix with water and it actually is on the surface of the hemoglobin molecule. But the people who have sickle cell disease, they put a valine amino acid in the same spot and valine does not like to mix with water. But the cell is done. Cell doesn't, the cell is just following orders, just following the instructions. So it puts the valine there for people who have sickle cell disease. The valine doesn't want to be there. It's surrounded by water and it's not happy. So what ends up happening is the amino acid molecule is all clumped together to try to bury their valine amino acids that are exposed on the surface to try to bury those valine amino acids away from the water. And if they clump together enough for people who have the disease, then they end up making the red blood cell have this weird shape which ends up making the red blood cells get caught in narrow blood vessels which causes this horrible disease. So this horrible disease is caused by a really tiny change in a very important molecule, but it's a tiny change that makes all of those things clump together because you went from a hydrophilic amino acid to a hydrophobic one. That's just one example of proteins clumping together or not folding properly that one example where diseases can be caused. There are other ones as well. There's muscular dystrophy is caused by a protein not being made properly and not holding up cystic fibrosis as well. There are many diseases like this. This is not the only one. Although I believe that sickle cell disease was the first disease that was understood at this level of detail. Prior to sickle cell disease, you might have a disease let's say in the 1920s. I know you have sickle cell disease or you have cystic fibrosis. Well, what's wrong with you? We don't know. We're just sick and your blood cells have a weird shape. This sickle cell disease was the first disease where people were actually able to find a specific molecule that was messed up that appeared to cause the disease. After that, then they also figured out specific molecules that were involved in cystic fibrosis and muscular dystrophy, but this was the first one that was understood. That's the end of this video. See you in the next one.