Alpha Helix Disruption - Video Tutorials & Practice Problems
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1
concept
Alpha Helix Disruption
Video duration:
7m
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Video transcript
Gonna talk about alpha helix disruption. So there are actually several factors that can disrupt alpha helices and prevent the formation of alpha helices. And we're gonna talk about 3 of them down below in our example, numbered 1, 2, and 3. And these correspond with the numbers that are down below in our example 123. And what you'll notice is that we've got a 4th 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, it, but we'll revisit it once we get here in our example below. So, number 1 says that alpha helices are typically found spanning, so they're found spanning the hydrophobic area within a membrane. So this isn't a full 100% requirement of alpha helices, but what we'll tend to see throughout our course is that, transmembrane proteins or proteins that span a membrane, within the hydrophobic region. So, this this region right here, this represents a lipid bilayer, and this is going to be the hydrophobic region. So, hydrophobic region. In this hydrophobic region, what we have is, the protein takes on an alpha helix conformation. But in the hydrophilic region, the water loving region which is right up above, these regions here do not form the alpha helices, and we'll see that's gonna be the case for a lot of different situations. And that's because hydrophilic environments, helix. And so instead of the backbone over here forming hydrogen bonds with itself to form the alpha helix, it forms hydrogen bonds with the neighboring water molecules instead. And that's why hydrophilic environments compete for hydrogen bond formation and disrupt alpha helices. So the second one is that alpha helices 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 r groups such as tryptophan's r groups, if you had a bunch of tryptophans in a row, then there would be a lot of steric hindrance between those r groups, and that might destabilize the alpha helix structure. And the same goes with the charged groups. And so, in our example down below, we're showing that how the pH of the solution and, charged r groups can actually destabilize the alpha helix structure through repulsions. And so we can see that through polyglutamate, which is shown here, all polyglutamate is is a protein that contains only glutamate amino acid residues, and then also polylysine which is below. And so on this graph over here, all it's showing 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 alpha helix. And so, this blue curve that's on here represents the, structure for polyglutamate. And notice that when polyglutamate is at low p h's, basically p h is below this range right here, that the polyglutamate is able to take on the alpha helix structure. However, as soon as you raise the pH above, this pH right here, notice that the structure of, polyglutamate changes from the alpha helix to a random confirmation. And that's because once it reaches this pH right here, any pH above that, glutamate r groups are going to be charged, negatively charged. And when all of these glutamates here are negatively charged, they're gonna repel each other. And when they repel each other, they're gonna take on a random confirmation instead of taking on the alpha helix confirmation. And that's really all this is trying to say. And so the same applies for polylysine which is down below. With the polylysine which only has a bunch of lysines, 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 alpha helix structure. But once the pH goes below this pH right here on the x axis, basically, what that's saying is that it's going to 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, lysine is gonna be in its conjugate acid form, which is gonna have positive charges, and all of these positive charges right next to each other are gonna repel each other and that's gonna destabilize the alpha helix structure. So again, all number 2 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 alpha helix structure. And so the third and final, new factor that we're gonna talk about is that all alpha 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 chirality of the amino acid residues. And so if you, know that all residues must have the same configuration, configuration of just a single residue, can actually disrupt the structure of the alpha helix. So remember that, most, that life predominantly uses l amino acids, not d amino acids. So if you were to have a d amino acid, in your alpha helix structure, then that could disrupt the alpha helix structure. And so that's all number 3 is saying. And then of course, our 4th factor here, which which we kinda already know about, is just taking into account the dipole of the amino of the alpha helix. So remember that the amino terminus over here has a partial positive charge, and the carboxyl terminus, which is over here, has a partial negative negative charge, which is right here. And so we already know that if we put, negatively charged amino acids by the, amino end, that's gonna create a stabilizing effect. But if we put positively charged, like charges, on the amino terminal of of the alpha helix, that's gonna create a destabilizing effect. So we kinda already talked about this previously, and the opposite applies for the carboxyl end. If we put negatively charged amino acid residues by the carboxyl end of the, alpha helix, that's gonna be destabilizing. That's gonna disrupt the structure because like charges repel one another. But if we put a positive charge over here, that's going to, promote the structure and create a stabilizing effect. So, that's all number 4 is saying. So, this concludes our lessons on the disruption of alpha helices and we'll talk about our final, our 5th and final factor disrupting alpha helices 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.
2
Problem
Problem
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.
3
concept
Alpha Helix Disruption
Video duration:
4m
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Video transcript
So the last factor that we're gonna talk about for alpha helix disruption is the idea that glycine and proline residues disrupt alpha helices. So we already know that alpha helix formation requires a very particular set of phi and side bond angles and they need these phi and psi bond angles to stabilize the required hydrogen bonds for alpha helix formation. And so, we already know that alpha helix bond angles appear in the lower left hand quadrant of the Ramachandran plot. And so down below, what you'll see is that we've got our alpha alpha 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, glycine and proline residues disrupt alpha helices. So this is the biggest thing that they destabilize alpha helices and they destabilize them for different reasons. Glycine's r group is literally just a hydrogen, so it's just simply too small and it's so small that steric hindrance cannot limit its bond angles enough to conform to the alpha helix bond angles. And then proline's residue, the major reason why proline disrupts, alpha helices is because it literally lacks a hydrogen atom on its amino group, for forming hydrogen bonds. And so that ends up creating a kink in the alpha helix chain. And so it turns out that prolines are actually way more disruptive than glycines. Glycines are disruptive to alpha helices, but not nearly as much as prolines. Prolines are like alpha helix murderers. They do not like alpha helices and you will almost never find prolines in alpha helices. And so, in our example below, we're gonna talk about how glycine and proline disrupt alpha helices just by looking at their plots. So over here on the far left, notice that we this is the typical Ramachandran plot of most amino acids and notice that the alpha helix is falling into the lower left quadrant just like we said earlier. And this is the right handed, alpha helix. The left handed alpha helix, remember, is super rare and it falls into the upper right quadrant. But, regardless of which alpha helix we're talking about, if we take a look at glycine's Ramachandran plot, which is over here in the middle, remember that it has permissible bond angles in all four quadrants. And so, when you look at these, regions right here where the alpha helices fall, you'll see that, it's really hard to restrict glycine to these particular, red regions that are here because glycine has all of these other permissible regions that are over here. So, why wouldn't it want to take on this conformation over this conformation over here? So, that is, why it's hard for, glycines to be found in alpha helix structures. Now if we take a look at proline, proline's are the Ramachandran plot is over here. And what you'll see is that for the left handed alpha helices, proline does not have any permissible angles to allow for that confirmation. Now, for the right handed alpha helices, 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, alpha helix region right there, but there are some, permissible regions. So really, it's not, the bond angles that are the major reason for why prolines are, really, disruptive to alpha helices. The major reason for why prolines are disruptive helices is because they literally lack a hydrogen atom that's required for hydrogen bonding. So remember that its amino group lacks a hydrogen atom because of its cyclic r group that attaches right back up to its, 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 glycine and proline are disruptive of Amina of alpha helices, but prolines are even more disruptive than glycines. So, we'll be able to apply these concepts in our practice problems, so I'll see you guys there.
4
Problem
Problem
An α-helix would be destabilized most by:
A
DNA missense mutation leading to a Gly residue placed in the α-helix sequence.
B
Interactions between neighboring Asp & Arg residues.
C
A hydrophobic environment competing for hydrogen bonds.
D
DNA missense mutation leading to a Pro residue placed in the α-helix sequence.
E
A net electric dipole spanning several peptide bonds throughout the α-helix.
5
Problem
Problem
At pH 6.8, which of the following peptides is least likely to form an α-helix?