going to talk about Alfa Helix disruption. So there are actually several factors that can disrupt Alfa Hillis ease and prevent the formation of Alfa jealousies, and we're gonna talk about three of them down below. In our example Number 12 and three. And these correspond with numbers that air down below and our example 12 and three. And what you'll notice is that we've got 1/4 factor here that's not listed up above. And that's because we kind of already talked about it in our previous videos. So it's not gonna be really much new information to you guys, and so we'll revisit it, but we'll revisit it once we get here, in our example below. So Number one says that Alfa Ulysses are typically found spanning, so they're found spanning the hydrophobic area within a membrane. So this isn't, ah full 100% requirement of Alfa Ulysses. But what will tend to see throughout our course is that, uh, trans membrane proteins or proteins that span a membrane within the hydrophobic region. So this this region right here, this represents a lipid bi layer, and this is going to be the hydrophobic region. So hydro phobic region in this hydrophobic region. What we have is, uh, the protein takes on an Alfa Helix confirmation. But in the hydro Filic region, the water loving region which is right up above these regions here, do not form the Alfa Hillis ease and we'll see. That's gonna be the case for a lot of different situations. And that's because hydro filic environments again these water loving environments here, here and here they compete for hydrogen bomb information in the Alfa Helix. And so instead of the backbone over here, forming hydrogen bonds with itself to form the Alfa Helix, it forms hydrogen bonds with the neighboring water molecules instead. And that's why Hydra Filic environments compete for hydrogen bond formacion and disrupt Alfa Ulysses. So the second one is that Alfa he leases are quite sensitive, and they're sensitive to destabilizing interactions between neighboring amino acid residues. So if you have a bunch of bulky residues right next to each other, bulky residues meaning really big are groups such as trip to fans are groups. If you had a bunch of trip to fans in a row, then there would be a lot of stare. Kendrick's between those are groups, and that might destabilize the Alfa Helix structure. And the same goes with the charge groups. And so, in our example down below, we're showing that how the pH of the solution and charged are groups can actually destabilize the Alfa Helix structure through repulsion. And so we can see that through Polly Glutamate, which is shown here. All Polly glutamate is is a protein that contains Onley, glutamate, amino acid residues and then also Polly listen, which is below and so on. This graph over here, all it's showing it is the pH on the X axis and then on the Y axis. We have specific rotation, but really you don't need to know about specific rotation. It's just saying it's just measuring the structure of the Alfa Helix. And so this blue curve that's on here represents the structure for Polly Glutamate and noticed that when Polly glutamate is at low, pH is basically Ph is below this range right here that the poly glutamate is able to take on the Alfa helix structure. However, as soon as you raise the pH above, Uh, this pH right here noticed that the structure of Polly glutamate changes from the Alfa. He looks to a random confirmation. And that's because once it reaches this pH. Right here, any pH above that glutamate are groups are going to be charged, negatively charged. And when all of these glue teammates here are negatively charged, they're gonna repel each other when they repel each other. They're gonna take on a random confirmation instead of taking on the Alfa Helix confirmation. And that's really all this is trying to say. And so the same applies for Polly. Listen, which is down below with the poly. Listen, which on Lee has a bunch of life signs that corresponds to the red And so notice that when the pH is above a certain region so above this pH. Right here it corresponds with an Alfa helix structure. But once the pH goes below this pH right here on the X axis, basically what that saying is that it's going toe lose its structure, and it takes on a random confirmation, which is down below. And that's again because at this ph below that pH listen is gonna be in its conjugate acid for him, which is gonna have positive charges in all of these positive charges right next to each other are gonna repel each other, and that's going to destabilize the Alfa Helix structure. So again, all number two is saying is that if you have too many charged groups right next to each other at a certain PH that's going to disrupt the Alfa Helix structure. And so the third and final, um uh, new factor that we're going to talk about is that all Alfa Helix residues must have the same configuration. They must have the same configuration and so down below. What you can see is that remember, the configuration is referring to the Chire ality of the amino acid residues. And so if you, um uh, no, that all residues must have the same configuration. Then you'll know that by changing the configuration of just a single residue, uh, can actually disrupt the structure of the Alfa Helix. So remember that, uh, most, um, that life predominantly uses l amino acids, not D amino acids. So if you were to have a d amino acid, um, in your alfa helix structure, then that could disrupt the Alfa Helix structure. And so that's all Number Three is saying and then, of course, our fourth factor here, which we kind of already know about, is just taking into account the DYP hole of the amino of the Alfa Helix. So remember that the amino terminus over here has a partial positive charge. And the car boxful terminus, which is over here, has a partial negative charge, which is right here. And so we already know that if we put, uh, negatively charged amino acids by the amino and that's gonna create a stabilizing effect. But if we put positively charged like charges on the amino terminal of the Alfa Helix, that's gonna create a destabilizing effect. So we kind of already talked about this previously. And the opposite applies for the car box will end if we put negatively charged amino acid residues by the car box will end of the Alfa Helix. That's gonna be destabilizing. That's going to disrupt the structure because, like charges repel one another. But if we put a positive charge over here, that's going to, uh, promote the structure and create s stabilizing effect. So that's all Number Four is saying. So this concludes our lessons on the disruption of Alfa jealousies and we'll talk about our final, our fifth and final factor disrupting Alfa jealousies and our next lesson video. But first, we're gonna get some practice with these four factors, so I'll see you guys in that practice video.
Why does poly-L-Glutamate adopt an α-helical structure at low pH but a random conformation above pH 5?
< pH 5, the (+) Glu repulsion destabilizes α-helices.
Alpha Helix Disruption
Play a video:
Was this helpful?
So the last factor that we're going to talk about for Alfa Helix disruption is the idea that glazing and pro lean residues disrupt Alfa. He'll seize. So we already know. The Alfa Helix formation requires a very particular set of fi and side bond angles, and they need these fine side bond angles to stabilize the required hydrogen bonds for Alfa Helix formation. And so we already know that Alfa Helix Bond angles appear in the lower left hand quadrant of the Rama Condron plot and so down below. What you'll see is that we've got our Alfa helix appearing in the lower left hand quadrant. Now, the major idea that I want you guys to know from this video is again that glazing and prowling residues disrupt Alfa. He'll see. So this is the biggest thing that they destabilized. Alfa Hillis ease, and they destabilize them for different reasons. Glistens. Our group is literally just a hydrogen, so it's just simply too small, and it's so small that Starik hundreds cannot limit its bond angles enough to conform to the Alfa Helix bond angles and then pro leans residue. The major reason for why pro lean disrupt um Alfa Hillis is is because it literally lacks ah, hydrogen atom on its amino group, um, for forming hydrogen bonds. And so that ends up creating a kink in the Alfa Helix chain. And so it turns out that pro leans are actually way more disruptive than glistens, glistens, air, disruptive toe, Alfa Ulysses. But not nearly as much as pro leans pro leans air like Alfa Helix murderers. They do not like Alfa Ulysses, and you will almost never find pro leans in Alfa Healy sees. And so, in our example below we're gonna talk about how glazing and paroling disrupt Alfa Ulysses just by looking at their Rama Condron plots. So over here on the far left notice that this is the typical Rama Condron plot of most amino acids and noticed that the Alfa Helix is falling into the lower left quadrant just like we said earlier. And this is the right handed, um, Alfa Helix. The left handed Alfa Helix, remember, is super rare, and it falls into the upper right quadrant. But regardless of which Alfa helix we're talking about, if we take a look at glistens Ramachandran plot, which is over here in the middle. Uh, remember that it has permissible bond angles in all four quadrants. And so when you look at these regions right here, where the Alfa Hillis is fall, you'll see that it's really hard to restrict glazing to these particular red regions that air here because glazing has all of these other permissible regions that are over here. So why wouldn't it want to take on this confirmation over this confirmation over here? So that is why it's hard for, um, glistens to be found in Alfa Helix Structures. Now, if we take a look at pro lean, pro leans are Rama Condron. Plot is over here, and what you'll see is that for the left handed Alfa Ulysses, Pro Lean does not have any permissible angles to allow for that confirmation. Now for the right handed Alfa Ulysses, you'll see that there it seems to be a little bit of overlap. It's not. There's not any dark regions that cover this, um, Alfa Helix region right there, But there are some permissible region. So, really, it's not the bond angles that air. The major reason for why pro leans are, uh, really disruptive toe Alfa Ulysses, the major reason for why Pro leans air disruptive toe Alfa Ulysses is because they literally lack, ah, hydrogen atom that's required for hydrogen bonding. So remember that it's amino Group lacks, ah, hydrogen atom because of its cyclic. Our group. That attach is right back up to its, um, amino group. And so that's the major reason. And so again, the biggest conclusion that I want you guys to get from this is that both glazing and pro lean are disruptive of Amina of Alfa Ulysses. But pro leans are even Mawr disruptive, thankless scenes. So we'll be able to apply these concepts and our practice problems, so I'll see you guys there.
An α-helix would be destabilized most by:
DNA missense mutation leading to a Gly residue placed in the α-helix sequence.
Interactions between neighboring Asp & Arg residues.
A hydrophobic environment competing for hydrogen bonds.
DNA missense mutation leading to a Pro residue placed in the α-helix sequence.
A net electric dipole spanning several peptide bonds throughout the α-helix.
At pH 6.8, which of the following peptides is least likely to form an α-helix?