Alpha Helix Hydrogen Bonding - Online Tutor, Practice Problems & Exam Prep

Alpha helices are stabilized by intrachain hydrogen bonds between the amino and carbonyl groups in the peptide backbone, specifically between residues x and x+4 or x and x-4. This results in a net dipole, with a positive charge at the N-terminus and a negative charge at the C-terminus, due to the orientation of polar peptide bonds. The total number of hydrogen bonds in an alpha helix is the number of residues minus four. Understanding these interactions is crucial for grasping protein structure and function.

Alpha Helix Hydrogen Bonding

In this video, we're going to talk about alpha helix hydrogen bonding. As you guys already know, alpha helices are stabilized by intrachain hydrogen bonds. Recall that by intrachain, we mean these hydrogen bonds form within the same single polypeptide chain, and no multiple polypeptide chains are involved with stabilizing an alpha helix. These hydrogen bonds form between the amino and the carbonyl groups in the peptide backbone. This means that the r groups of amino acids are not involved with the hydrogen bonding that stabilizes an alpha helix. This point applies not only to alpha helices but also to other secondary structures as well, such as beta sheets, which we'll talk about later in our course.

Now, these next two bullet points are dedicated to telling us how alpha helix hydrogen bonding works. The carbonyl group of an amino acid residue in an alpha helix will hydrogen bond to the amino group that is 4 residues away towards the C-terminal end of the peptide. Another way to say the same thing is that the carbonyl group of residue x will hydrogen bond to the amino group of residue x+4 away towards the C-terminal end. This also applies for the amino groups, where the amino group of an amino acid residue in an alpha helix will hydrogen bond to the carbonyl group of a residue x-4 away towards the N-terminal end of the peptide.

Essentially, we're saying the carbonyl group of an amino acid residue in an alpha helix will hydrogen bond to the amino group of a residue x+4 away towards the C-terminal end. The amino group of an amino acid residue, which contains a nitrogen atom, will hydrogen bond to the residue that is x-4 away towards the N-terminal end. The N in the amino group can remind you of the negative sign in the x-4, distinguishing it from the x+4 in the carbonyl group.

Because alpha helix hydrogen bonding works in this fashion, both the first and the last four amino acid residues of an alpha helix will not fully participate in alpha helix hydrogen bonding. We'll understand how this works better in the example below of alpha helix hydrogen bonding.

In this example, we have a hexapeptide or a peptide with 6 amino acid residues, evidenced by the 6 different R groups throughout our peptide. Notice that the left side is the amino terminal with the free amino group, and the right side is the C-terminal with the free carboxylate group. The way that the hydrogen bonding works is that the carbonyl group of an amino acid residue will hydrogen bond to the amino group of a residue x+4 away. This is shown by the pink line being highlighted in green. Conversely, the amino group will hydrogen bond to the carbonyl group of a residue x-4 away.

The first and the last four amino acid residues do not fully participate in alpha helix hydrogen bonding. Consequently, the total number of hydrogen bonds in an alpha helix equals the number of amino acid residues participating in the alpha helix minus the number four. Since we have 6 amino acid residues and subtract 4, we have a total of 2 hydrogen bonds in this alpha helix, both shown in pink.

Moving forward, we'll be able to get some practice utilizing these concepts in this video, and I'll see you guys in our next example video.

Alpha Helix Hydrogen Bonding Example

Alright. So this example problem asks, which residue does the carbonyl group of the 21st residue in a 30 residue alpha helix hydrogen bond to? And so down below, I've drawn an alpha helix, and we know that this alpha helix has a total of 30 amino acid residues in it. We are specifically being asked about the 21st residue. So let's imagine that the 21st residue is somewhere at this position here on our alpha helix. Notice that we are specifically being asked about the carbonyl group of this 21st residue.

Recall from our previous lesson videos that the carbonyl group of an amino acid residue in an alpha helix will hydrogen bond to the residue that is \( x + 4 \) away towards the C-terminal end. Because we are not being asked about the amino group, we will not use \( x - 4 \) here for this problem. So we can go ahead and cross this portion off.

Therefore, since our \( x \) here refers to the 21st residue, we can essentially bring that over here; we take our 21st residue and add 4 to it, \( 21 + 4 \), that gives us 25. This equation is our answer and essentially what we are saying is that the carbonyl group of the 21st residue will hydrogen bond to the amino group of the 25th residue. Option A here is the correct answer.

We can go ahead and indicate it as being correct. That concludes this example problem, and I'll see you guys in our practice videos.

The oxygen-storage protein myoglobin has 8 α-helices in its single polypeptide chain. Its 67^th residue is near the center of a 19 residue α-helix. Which residue does the amino group of myoglobin's 67^th residue hydrogen bond to?

• A. 63rd residue
• B. 64th residue
• C. 71st residue
• D. 72nd residue

Alpha Helix Hydrogen Bonding

So now that we know how alpha helix hydrogen bonding works, let's talk about alpha helix net dipoles. Alpha helices have an overall net dipole, and this is due to the fact that the direction of all the polar peptide bonds are forced to face the same direction because of all the interchain hydrogen bonds. We'll be able to see how this works down below, but essentially what's happening is that there's a net electron density being shifted towards the C-terminus end, the carboxyl terminus. Negative charges are going towards the C-terminus. This means that the N-terminus of the alpha helix will result in a net positive charge, whereas the C-terminus will end up having a net negative charge.

Let's take a look at our example down below of the alpha helix net dipole. What we have is our right-handed alpha helix here and the peptide bonds, notice, are all highlighted in pink. You can see that for all of these peptide bonds shown here, all of them have the terminus end facing towards the C-terminus end. The carbonyl group, remember, has a net negative charge on it. You've got a net negative charge pointing towards the C-terminus end. Essentially, what we've got is a net dipole going in this direction. Negative charges, essentially pointing towards this end, plus for all of these hydrogen bonds – hydrogen bonds that are forming here, shown in yellow – essentially, electron density of the carbonyl group is being donated upwards to the amino group above. You have this shift in electron density towards the carboxyl terminus. Over here towards the carboxyl terminus, we have a net negative charge. That means that the amino terminus, on the other hand, is going to be left with a net positive charge. Again, this has to do with the hydrogen bonding orienting the carbonyl groups of all the peptide bonds in the same exact orientation and over a net effect of all of these peptide bonds that creates the overall net dipole that we see with alpha helices.

This net dipole is a really unique feature of alpha helices, so it's important to keep that in mind because we don't really see this dipole with other secondary structures like beta sheets, for instance. That's something important to keep in mind. We'll be able to get some practice utilizing these concepts in our practice videos, so I'll see you guys in those videos.

True or False: Negatively charged residues near the α-helix N-terminal are stabilizing due to its net dipole.

• A. True
• B. False

Triose phosphate isomerase (TPI) is a crucial enzyme involved in the glycolysis pathway and contains 14 α-helices. Considering the net dipole of the α-helix, which of the following would be most destabilizing to TPI's structure?

• A. An electric dipole spanning several peptide bonds throughout its α-helices.
• B. The presence of Glu residues near the N-terminus of its α-helices.
• C. The presence of Arg residues near the C-terminus of its α-helices.
• D. The presence of Lys residues near the N-terminus of its α-helices.

The hemagglutinin protein in influenza virus contains a remarkably long α-helix with 53 residues.

A. How long is the α-helix? _____________

B. How many turns does this α-helix have? _____________

C. How many hydrogen bonds are present in this α-helix? ______________

So here's a 3-part practice problem, and it says the hemagglutinin protein and influenza virus contains a remarkably long alpha helix with 53 residues in it. And part A asks, how long is the alpha helix? And recall that the way that we measure the length of an alpha helix is simply by taking the total number of amino acid residues, which is given to us as 53 amino acids, and we multiply this by the rise of the alpha helix. And recall, the alpha helix rise is the length, per amino acid residue and that's just a small number of 1.5 Ångströms. And so, if we take our calculator and do 53 times 1.5, that gives us our answer of 79.5 Ångströms. And so, that is our answer for part A, 79.5 Ångströms. Now, part B asks, how many turns does the alpha helix actually have? And so, to answer this, we're going to need to remember that in one turn of the alpha helix, there are 3.6 amino acid residues. And so, if we take our total amount of amino acid residues, so total amount of amino acid residues is 53, and we divide that by 3.6 residues per turn, then what we'll get is the number of turns. So if you take 53 and divide it by 3.6 in your calculator, what you'll end up getting is 14.7 turns and that is our answer, so we can put that over here in this blank. Now, the last part, part C, asks how many hydrogen bonds are present in the alpha helix? And recall that, the way that alpha helix hydrogen bonding works is that the first and last four amino acid residues in the alpha helix do not fully participate in hydrogen bonding. So, 4 here is our magic number and it turns out that the way the alpha helix hydrogen bonding works, that the number of hydrogen bonds, so number of hydrogen bonds, is always going to be equal to the total number of amino acid residues, which is given to us as 53. So it's always going to be equal to the total number of amino acid residues minus our magic number 4. And so, that means that we're going to have a total of 49 hydrogen bonds, 49 hydrogen bonds in our alpha helix. And so, our answer up here is just going to be 49 hydrogen bonds. And so, that concludes this practice problem, and I'll see you guys in our next one.

Which of the following statements about α-helices is false?

• A. Myoglobin & hemoglobin α-helices are right-handed α-helices.
• B. Each residue of an α-helix creates a 100˚ turn of the α-helix backbone.
• C. The core of an α-helix is tightly packed with backbone atoms.
• D. α-helices have an overall macrodipole with a partially positive C-terminus & partially negative N-terminus.
• E. Hydrogen bonds that hold the α-helix together are about parallel to the axis of the helix.

Here’s what students ask on this topic:

What stabilizes the alpha helix structure in proteins?

The alpha helix structure in proteins is stabilized by intrachain hydrogen bonds. These hydrogen bonds form between the amino and carbonyl groups in the peptide backbone. Specifically, the carbonyl group of an amino acid residue forms a hydrogen bond with the amino group of a residue that is four positions away (x+4) towards the C-terminus. This pattern of hydrogen bonding helps maintain the helical structure and is crucial for the stability of the alpha helix. The R groups of the amino acids do not participate in these hydrogen bonds.

How does hydrogen bonding occur in an alpha helix?

In an alpha helix, hydrogen bonding occurs between the carbonyl group of one amino acid residue and the amino group of another residue that is four positions away (x+4) towards the C-terminus. Conversely, the amino group of an amino acid residue will hydrogen bond to the carbonyl group of a residue that is four positions away (x-4) towards the N-terminus. This pattern of hydrogen bonding is consistent throughout the helix, stabilizing its structure. The first and last four residues of the helix do not fully participate in hydrogen bonding, which affects the total number of hydrogen bonds in the helix.

What is the net dipole of an alpha helix and how is it formed?

The net dipole of an alpha helix is formed due to the orientation of polar peptide bonds, which are all aligned in the same direction because of intrachain hydrogen bonding. This alignment causes a shift in electron density towards the C-terminus, resulting in a net negative charge at the C-terminus and a net positive charge at the N-terminus. This unique feature of alpha helices is not observed in other secondary structures like beta sheets. The net dipole is important for the function and interaction of proteins.

Why do the first and last four residues of an alpha helix not fully participate in hydrogen bonding?

The first and last four residues of an alpha helix do not fully participate in hydrogen bonding because there are not enough residues on either end to form the necessary hydrogen bonds. For a residue to participate in hydrogen bonding, it needs to be able to bond with another residue that is four positions away. Since the ends of the helix lack these neighboring residues, they cannot form the complete set of hydrogen bonds, resulting in partial participation.

How do you calculate the total number of hydrogen bonds in an alpha helix?

The total number of hydrogen bonds in an alpha helix can be calculated by subtracting four from the total number of amino acid residues in the helix. This is because the first and last four residues do not fully participate in hydrogen bonding. For example, if an alpha helix has six amino acid residues, the total number of hydrogen bonds would be 6 - 4 = 2. This formula helps in understanding the stability and structure of the alpha helix.