Altering Primary Protein Structure - Online Tutor, Practice Problems & Exam Prep

Altering primary protein structure involves changing the amino acid composition or sequence, which can significantly impact a protein's shape and function. A single amino acid substitution may not always lead to drastic changes, especially if the substitute shares similar properties. For example, substituting valine with isoleucine, both non-polar amino acids, is less likely to affect the protein's overall conformation. Understanding these interactions is crucial for grasping protein functionality and stability in biological systems.

Altering Primary Protein Structure

In this video, we're going to talk about altering the primary protein structure. Recall that the primary protein structure consists of both the amino acid composition and the sequence of amino acid residues in a chain from the N-terminal end to the C-terminal end. And because that's true, the primary protein structure can actually be altered by changing either the composition or the sequence. It doesn't matter which one you change. If you change one or the other, you're going to be changing the primary protein structure. It's really interesting because proteins are so sensitive that all it takes is just a single amino acid change, and that could potentially cause a protein to lose its shape and function. So it's not guaranteed that a single amino acid change will change the protein's shape and function, but it could. Most proteins have thousands of amino acids in them, so they're pretty long proteins in nature. But changing just one amino acid could change the overall shape and structure for all 1,000 of those amino acids. So you can see how sensitive a protein's shape and structure is to the primary protein structure. And so, down below, what we have is a diagram showing you how the primary protein structure can be altered. At the very top, what we have is the original primary structure of a protein in this blue box way up here. And so notice that the original sequence is just methionine, valine, glycine, phenylalanine, alanine, and glycine from the N-terminal to the C-terminal.

There are two ways to change the primary protein structure. The first is to change the composition. There are really two ways to change the composition. You can either remove or add amino acids, or you could substitute amino acids. When you remove or add amino acids, the composition can be seen in this example here, where we've removed the very end amino acids. So, we've taken this glycine and removed it from the sequence. Notice that the glycine is no longer here. That is one way to change the composition. The sequence or the order of amino acids is still pretty much the same. It's just that we've removed the one at the end. This is still considered a change in the primary protein structure. The same goes for substituting amino acids. Here we have a phenylalanine and it's been substituted with an aspartic acid. That is an example of a substitution, and we're changing the composition. We're also arguably changing the sequence by making an amino acid substitution because the order is not the same. So there are those slight differences between them.

The second way to change the primary protein structure is to change the sequence. Remember, the sequence is the specific order of amino acids. If we change the sequence, the way to change the sequence is to just rearrange the amino acids. If you have the same composition, we're not changing the composition here, but we're rearranging the amino acids. So it's the same number and the same types of amino acids in this example down here. It's just that we've changed the order. So instead of methionine coming first, we have phenylalanine coming first. By rearranging them, that's an example of changing the sequence but not changing the composition. Basically, either a change to the composition or sequence will alter the primary protein structure, and altering the primary protein structure either may or may not alter the protein's final shape or function. It's going to depend from situation to situation and from protein to protein. Just keep in mind that it could cause the protein to change shape or function. This concludes this lesson here, and I'll see you guys in our practice video.

True or false: The following proteins with identical composition are certain to have the same shape/function.

Protein #1: L-G-T-V-R-D                        Protein # 2: D-R-V-T-G-L

• A. True
• B. False

Altering Primary Protein Structure

In this video, we're going to talk about substituting amino acids. It's interesting because if the substitute amino acid has similar properties to the original amino acid that's being replaced, then it's actually going to be less likely to cause a drastic change. Perhaps, the protein will retain its overall shape and its function if you substitute with an amino acid that has similar properties. Let's take a look at our example below, which asks, which amino acid substitute is least likely to impact the protein shape and function if it's substituted with valine. Here we have our protein and notice that the valine here is right here. Below are our options for substituting with valine. Basically, the strategy for this is to remember our groupings and our mnemonics for grouping the amino acids. Remember, for the non-polar amino acids, it's GAVLYMP. Valine here, its one-letter code is V, and so it falls into the GAVLYMP. It's right here as valine, a non-polar amino acid. If we're trying to have the least likelihood of impacting the protein shape and function with this substitution, we're going to want the amino acid to be a non-polar amino acid. Looking at these answer options down below, what you'll see is that aspartic acid, which is D, is a negatively charged acidic amino acid, as is glutamic acid, which is also down here. Histidine is H, which is a positively charged amino acid. The only one that falls under the non-polar amino acid category is isoleucine, which is up here. They both fall into the same category. This means that isoleucine, of these four options, is going to be the one that's going to be least likely to impact the protein's overall shape and function if it's substituted with the valine here. This concludes this lesson, and I'll see you guys in our practice videos where we're going to be able to get some practice with this. See you there.

Which amino acid is least likely to alter protein shape/function if substituted with an Arg residue?

• A. Lys
• B. Tyr
• C. Asn
• D. Ala

Patients with sickle-cell anemia disease have a point mutation leading to a single amino acid substitution in the hemoglobin protein, causing it to alter its shape/function. Which amino acid substitution most likely causes the disease?

• A. Ser to Thr
• B. Arg to Lys
• C. Val to Leu
• D. Glu to Val

Here’s what students ask on this topic:

What is primary protein structure and how can it be altered?

Primary protein structure refers to the linear sequence of amino acids in a polypeptide chain, from the N-terminal end to the C-terminal end. It can be altered by changing either the amino acid composition or the sequence. Altering the composition involves adding, removing, or substituting amino acids. Changing the sequence involves rearranging the order of amino acids without altering their types or numbers. These changes can significantly impact the protein's shape and function, as even a single amino acid substitution can potentially alter the protein's overall conformation and activity.

How does substituting amino acids affect protein structure and function?

Substituting amino acids can affect protein structure and function depending on the properties of the substituted amino acid. If the substitute has similar properties (e.g., polarity, charge) to the original amino acid, the impact on the protein's shape and function is likely to be minimal. For example, substituting valine (a non-polar amino acid) with isoleucine (also non-polar) is less likely to cause drastic changes. However, substituting with an amino acid of different properties (e.g., valine with aspartic acid, which is negatively charged) can significantly alter the protein's conformation and function.

What are the two main ways to change the primary protein structure?

The two main ways to change the primary protein structure are by altering the amino acid composition and by changing the sequence of amino acids. Altering the composition involves adding, removing, or substituting amino acids. Changing the sequence involves rearranging the order of amino acids without changing their types or numbers. Both methods can significantly impact the protein's overall shape and function, as the primary structure is crucial for determining the protein's final conformation and activity.

Why is a single amino acid change significant in proteins?

A single amino acid change is significant in proteins because it can alter the protein's overall shape and function. Proteins are highly sensitive to their primary structure, and even a minor change can disrupt the folding and stability of the protein. This can lead to loss of function or gain of a new, potentially harmful function. For example, a single amino acid substitution in hemoglobin can cause sickle cell anemia, demonstrating how critical the primary structure is to protein functionality.

How does the similarity of properties between substituted amino acids influence protein stability?

The similarity of properties between substituted amino acids influences protein stability by reducing the likelihood of drastic changes in the protein's shape and function. If the substituted amino acid has similar properties (e.g., polarity, charge, size) to the original, the protein is more likely to retain its original conformation and activity. For instance, substituting valine with isoleucine, both non-polar amino acids, is less likely to disrupt the protein's structure compared to substituting valine with a charged amino acid like aspartic acid.