Coiled-coil domain containing 18

Transcription

In this webcast, we’re going to look at protein domains consisting only of α helices. These are relatively few in number, and they are just two types of packing modes. One is known as the 4-helix bundle, and the second is known as the globin domain. Let’s take a look at a schematic picture, a cartoon diagram of the four-helix bundle. This is found in proteins like Cytochrome C. Let’s start at the N-terminus and represent the α helices as these red cylinders. As we travel around, we can see that basically these red cylinders pack together side by side and almost in a parallel-type fashion. Now, if we were to take a look at this from the top view down, what we’ll end up finding is that these proteins, these protein α helix ah, segments pack together in a way that creates an amphiphilic structure. So let’s number this. Number this in the same way that it follows the N to C sequence, and then look at the end on view and number the cylinders in the same way. So these cylinders go around in this direction, and what we can see are these green and red spheres. The green and red spheres are representing amino acid side chains. Remember when we talked about the α helix, that it has side chains that radiate from the center of the cylinder, and these side chains that are colored green and that come together in the core are mostly hydrophobic amino acids like leucine, valine, isoleucine, phenylalanine, alanine. And so in an aqueous solution, they’re basically trying to bury themselves in a way that can avoid being in contact with water. Then on the outer surface, there’s a set of amino acids that form the other half of the α helix face that’s exposed to water. So what you can see is the polar amino acid side chains that are going to be charged or have hydroxyl groups are going to be, ah, able to solubilize the protein because they’ll be in contact with the water, leaving the dense hydrophobic core to provide stability for the formation of this four-helix bundle. All together, we see that this has a very nice amphiphilic kind of structure, and so this theme that proteins, ah, fold into, ah, amphiphilic kinds of structure is born out from the Cytochrome C structure or the four-helix bundle that we see here. Let’s take a look at the globin domain. The globin domain consists of eight or more different α helices and notice how now they’re not parallel at all. They pack together in this sort of crisscrossed way. And the main thing I want to draw your attention to is how they can form a pocket, and they form a pocket that will house, in this case, a heme, a heme porphyrin. A heme porphyrin is an iron atom that basically is able to bind oxygen. The main point I want to draw your attention to is that radiating from cylinder F and E are two different, ah, imidazole groups that come from the histidine amino acid. And remember the structure of, ah, the histidine amino acid? Those imidazole rings have nitrogen atoms that can coordinate and bind to the Lewis acidic iron atom and hold that porphyrin, ah, that, that I’ll color for you green. There it is. Those are the atoms of the porphyrin. It’s sandwiched in that pocket, and it’s held in place by those imidazole rings of histidine. Let’s take a look at the three-dimensional structure. First, let’s take a look at the Cytochrome C. The four different helices are colored for you there. Cytochrome C also has an iron porphyrin, and you can see the iron atom right there. I won’t show you the imidazole side chains, but they’re there binding that iron as well. Here’s a structure of hemoglobin. Hemoglobin has actually four different, ah, chain molecules, and you can see the four different porphyrins. Actually, you can see two of them here, and I’ll spin this around, and hopefully, we can get another view of that. And so there’s some of the other chains that you see as well. Now if we look at one individual chain, then it’s going to be, ah, the so-called monomeric unit. It’s going to look like that, and I’ve colored for you one of the chains, one of the α-helix segments of the globin domain. We can examine this a little bit more closely. So here’s a-a-a series of pictures where we’re going to look at the porphyrin. And notice the iron atom right there. And what I will do is I’ll spin this around, and you’ll see a series of different pictures where now you can see the 5-membered ring of that imidazole that forms the histidine amino acid radiating outward from this blue α helix. So the protein provides a scaffold that fixes the histi- the, ah, the histidines in just the right way that they can bind that, ah, that iron porphyrin in place. I’ll spin it around just a little bit more, and you’ll be able to see the 5-membered ring of the imidazole that’s coming from the histidine on this white α helix and how it, on either side, comes together to form this ah, pin to pin in place the, ah, the porphyrin molecule.