In this video, we're going to introduce the 4 types of lipid-linked membrane proteins. And so notice down below, we have this table right here that's giving you guys information on the 4 types of lipid-linked membrane proteins. But also notice that below the table, we have this image that is also showing you the 4 types of lipid-linked membrane proteins. And so the numbers that you see up above in our table right here correspond with the numbers that you see down below in our image. And so moving forward, we're first going to fill out our table and then after our table is filled out, we'll go back down and revisit this image down below to discuss that. Alright. So that being said, the 4 lipid linked membrane proteins are palmitoylated proteins, prenylated proteins, myristoylated proteins, and glycosylphosphatidylinositol or GPI linked proteins for short. And so these 4 lipid-linked membrane proteins differ from each other based on the lipid group that they're covalently attached to, the covalent linkage that links the lipid group to the protein and the modifications that they have, as well as by the side of the membrane that these Lipid Linked Membrane Proteins are found on, in terms of being found on the intracellular side of the membrane or on the extracellular side of the membrane. Now, the Lipid Linked Membrane proteins are actually named based on the specific lipid group that they are covalently attached to. For example, the Palmitoylated Proteins, as the name implies, are specifically linked to the fatty acid Palmitate. The prenylated proteins as the name implies with the prene are linked to isoprenoids, specifically farnesyl or geranyl groups, which we'll talk more about down below in our image once we get to it later in this video. And then, of course, the myristoylated proteins, as the name implies, are specifically linked to the fatty acid myristate, and the glycosylphosphatidylinositol or GPI linked proteins as the name implies are linked to the fatty acid phosphatidylinositol, which you might recall from our previous lesson videos is an example of a class of Glycerophospholipids. Now in terms of the covalent linkage that links the lipid group to the protein, notice that both the palmitoylated proteins and the prenylated proteins, which both start with the letter p, contain thiolinkages. And so recall that thiolinkages contain sulfur atoms. And the only amino acid residue that contains a sulfur atom in its r group is, of course, the amino acid residue, cysteine. And so they'll they are both, contain thiolinkages, with cysteine residues in them. Now, the palmitoylated proteins, specifically have a thioester link, whereas the prenylated proteins specifically have a thioether link. And we'll be able to distinguish between the Ester and the ether, again, down below in our image later when we get to it. Now, one thing that's important to note is that with the palmitoylated proteins, the thioester link can form with any cysteine residue that's found in the protein. And so there's no requirement for the c-terminal cysteine residue or the n-terminal cysteine residue. It's any cysteine residue. And this is very different from the prenylated proteins because the thioether linker in prenylated proteins forms specifically with the c-terminal cysteine residue. And also with prenylated proteins, there is a modification that takes place. And this modification includes the methylation of the carboxyl group or the c-terminal end. And recall, methylation just means adding a CH3 group. And again, we'll be able to visualize this in our image down below when we get to it. Now in terms of the myristoylated proteins and the glycosylphosphatidylinositol or the GPI linked proteins, which note that neither of these start with the letter p, Both of these have amide linkages and so we can put in amide here for both of them. Now in terms of the myristoylated proteins, they have an amide linkage specifically with the n-terminal glycine residue. Whereas the GPI linked proteins have an amide linkage specifically with the c-terminal end. And the c-terminal amide linkage is connected to the lipid group via a complex lipid anchor, which again we'll be able to visualize in our image down below. Now, in terms of the side of the membrane that each of these lipid-linked membrane proteins are found on, notice that the first three palmitoylated, prenylated, and myristoylated proteins are all found on the intracellular side of the membrane. And so we can write intracellular side here. And so these 3 here are, almost exclusively found on the intracellular side of the membrane. Whereas, the very last one, the GPI linked one is almost exclusively found on the extracellular side of the membrane, on the outside of the cell. And so now that we've completed our table up above, we can now take a look at our image down below. And so as a reminder, the numbers that we see in our table correspond with the numbers that we see down below in our image. And so the number 1 here corresponds with the palmitoylated proteins. And of course, as the name implies, palmitoylated proteins are covalently linked to the fatty acid palmitate. And notice that the protein that we have here, highlighted in yellow, has an amino end and a carboxyl end. And the protein is specifically linked to the palmitate fatty acid via a thioester linkage as we have highlighted here in blue. And notice that the thio, part is referring to the sulfur atom, and the only amino acid residue that contains a sulfur atom in its r group is the amino acid cysteine. And so notice that this cysteine is appearing really at any cysteine residue within the protein. It's not specifically the c, the n-terminal cysteine, or the c-terminal cysteine. It's really any internal cysteine residue within the protein. And of course, this is a thioester linkage here because recall that esters are going to have a carbonyl group like this. Linked to the sulfur atom and so, this is exactly the thioester that we were referring to up above in our table. And so if we go back up to revisit our table here, notice that this is exactly what we were saying. Palmitoylated proteins have a thioester linkage with any cysteine residue, not necessarily the n-terminal or c-terminal cysteine residue, any cysteine residue. And they're specifically linked to the fatty acid palmitate. And also notice that they're specifically found on the intracellular side of the membrane and so, looking down here, notice the intracellular side is down here whereas the extracellular side is up here. And so the first 3 of as we mentioned are found on the intracellular side whereas the last one is found on the extracellular side. Now, the number 2 that we have here is going to correspond with the prenylated protein and of course, the prene indicates that it's gonna be containing isoprenoids such as either farnesyl or geranyl whose structures we're showing you here. And these are really just the 2 most common isoprenoids that are linked in prenylated proteins. And so notice that the protein here has its amino group over here and so its carboxyl group is over here and its carboxyl group is actually involved with the linkage to the isoprenoid. And so this means that the sulfur atom here is going to be part of the c-terminal cysteine residue specifically. And notice that this sulfur is not forming an ester because there's no carbonyl group. Instead, the sulfur here is a thioether linkage and recall that ethers look like this with 2 R groups on either side. So, this is the ether. Whereas this over here is the ester. So, you can compare them side by side. And so also notice that this C-terminal end has a modification to it because it is being methylated and so we have a carboxyl, methyl group over here. And so the again, this is exactly what we said up above in our table. And so if we revisit it briefly, notice that the prenylated proteins are specifically linked to isoprenoids such as Farnesyl or Geranyl, and they contain a thioether link specifically to the c-terminal cysteine residue. And also the c-terminal and the carboxyl end is gonna have a modification with a methylation group, a CH3 group attached as we indicated, down below right here. Now, moving on, the third one here is, of course, going to be the myristoylated protein. And so, we can go ahead and put that here. And of course, the as the name implies, the myristoylated protein is going to be linked to the fatty acid myristate as we see. But notice that, the 2 previous ones, palmitoylated and prenolyted, both started with p's and both contained thiolinkages. Whereas, myristoylated does not contain a P, so it's not gonna contain a thiol linkage. Instead, it's gonna contain an amide linkage. As we see right here, right here, this is an amide linkage with the nitrogen atom and the, carbonyl group. And notice this time that the protein has its c-terminal and over here not involved with the linkage and instead, it's the n-terminal end here that is involved with the linkage to the fatty acid myristate. And notice specifically that the r group of this amino acid is a hydrogen atom, which means that this is specifically a glycine amino acid residue here at the end terminal end because of this hydrogen atom as the r group. And so, this is exactly what we mentioned up above in our table. Notice that the myristoylated proteins here are specifically linked to the fatty acid myristate and they have an amide linkage specifically with the n-terminal glycine residue. And again, they're also found on the intracellular side of the membrane along with the prenylated and palmitoylated proteins. Now, last but not least, we have number 4 here, which is gonna be our GPI linked protein. And of course, the GPI linked protein, we said specifically are linked to a phosphatidylinositol group, which we have right here. And recall, a phosphatidylinositol group is just a glycerophospholipid, one of the glycerophospholipids that we have highlighted right here. And of course, we also mentioned that, it's going to be the protein, which is noticed up above right here, is going to be linked via its C-terminal link. It's gonna be linked via C-terminal specifically by an amide linkage. And so here we have another amide linkage. Linking the C-terminal and to the fatty acid down here. And so, notice that in between here, we have this complex linkage, that we were referring to previously, this complex lipid anchor. And so really, we're not gonna get into the details of this complex lipid anchor here, but you can see that it does have a tetrasaccharide in it. And it also has this phosphoethanolamine group that you can see, right here. And specifically, the GPI linked proteins are found on the extracellular side of the membrane and so that's also important to note. And so this here concludes our, introduction to the 4 types of lipid linked membrane proteins and moving forward, we'll be able to get some practice applying the concepts that we've learned. And so I would recommend filling out this table a few times and closely comparing the table up above with the image down below to solidify these learning objectives. And so I'll see you guys in our next video.
