Protein Motifs and Domains - Online Tutor, Practice Problems & Exam Prep

Protein tertiary structure comprises motifs and domains, which are essential for understanding protein function. Motifs, or super secondary structures, are specific patterns of secondary structures like alpha helices and beta strands, serving various roles such as providing strength and creating binding sites. Domains are combinations of motifs that can independently fold and extend the peptide backbone. Recognizing these structures aids in predicting protein functions, as similar domains often indicate shared roles across different proteins.

Protein Motifs and Domains

So now that we've introduced tertiary structure, we can talk about protein motifs and domains. It turns out that tertiary protein structure actually includes the distribution of secondary structures such as alpha helices, beta strands, beta turns, and loops to make protein motifs and protein domains. Just to get you guys oriented on the hierarchy of all of these terms and structures, we've got this image below. Of course, at the lowest level of the hierarchy, composition, as well as amino acid sequence, and the sequence is the particular order of amino acids from the N-terminal to the C-terminal of a polypeptide chain.

Then, what we have is our secondary structures, and we talked about multiple types of secondary structures including alpha helices, beta sheets, and, loops and beta turns. Then what we did was we jumped straight from secondary structure to tertiary structure. Now that we've got tertiary structure introduced, we can better understand this organization. It turns out that secondary structures actually come together to form super secondary structures, which are also known as domains, which are just independent folding units.

Together, the motifs and the domains, as you can see by this bracket here, they come together to form the tertiary structure which we know as the overall three-dimensional shape of the protein. So, what we're going to do first is talk about the super secondary structures or the motifs, and then, once we're done talking about the motifs, we'll go and we'll talk about the protein domains. So, I'll see you guys in our next video where we'll talk about protein motifs.

Protein Motifs and Domains

So as we said in our previous video, motifs are also known as super secondary structures. And if you Google the definition of motif, what you'll find is that in the everyday language, it means a pattern, and that's really all a protein motif is. It's literally just a specific pattern and combination of secondary structures such as, for instance, alpha helices, beta strands, beta turns, and loops. And so, motifs can have varying functions or jobs in different proteins, and they can have different functions in proteins that include providing strength, as well as creating binding sites for different molecules. And it turns out that there are actually several hundred known motifs. And so it's not likely that your professor is going to want you to memorize all of them. So, there are a few common ones that you might want to know, and I've tried to provide those here. What you'll see is that we've got a helix-loop-helix motif, a coiled coil motif, a beta-alpha-beta motif, and a hairpin motif. In our example below, what we're going to do is label the corresponding motifs. For our first motif here, what we have is the helix-loop-helix motif. And literally, this is just an alpha helix, so notice it's an alpha helix with a loop and another alpha helix.

That's exactly a coiled coil. With the coiled coil, what you'll see is that it's two alpha helices that are actually wound up on one another. Remember that a single alpha helix is going to be an intrachain structure, so it's going to be within one single polypeptide chain. An alpha helix is different than a coiled coil because the alpha helix is a single polypeptide chain, whereas the coiled coil is two polypeptide chains, two alpha helix structures that are wound up and twisted on one another. This type of structure really does create a lot of strength. Whenever you see coiled coil structures, you know that that protein is going to provide a lot of strength.

The next motif that we have is the beta-alpha-beta motif. With this beta-alpha-beta motif, it's literally just a beta strand connected to an alpha helix which is connected to another beta strand, so it's beta-alpha-beta, pretty straightforward. Then our last and final motif is the hairpin motif. With the hairpin motif, it's literally just two beta strands going in antiparallel direction that's looped together by a hairpin loop. It's a small little hairpin loop that connects two beta strands that are antiparallel; they're going in opposite directions. These are some of the common motifs that you might want to try to commit to memory that your professor might try to ask you about. We'll be able to get a little bit of practice in our practice video, so I'll see you guys there.

Which of the following colored regions in the images below is not an example of a supersecondary structure?

• A. Greek key.
• B. β-meander.
• C. βαβ unit.
• D. Type I β-turn
• E. Helix-loop-helix

Protein Motifs and Domains

So now that we've talked about protein motifs, we can focus on protein domains. Domains are really just combinations of motifs. Again, motifs are patterns and combinations of secondary structures, and domains are combinations of motifs, so you can see how that hierarchy builds up on itself. The interesting thing about domains is that they are independently folding units. They have the ability to independently fold from the rest of the protein. Domains have the potential to be an extension to the peptide's backbone, and can be found on a single polypeptide chain. One single polypeptide chain could have multiple domains because a domain is just an extension to the peptide backbone. It's really important not to confuse domains with subunits. Subunits, which we will talk more about when we get to quaternary structure later in the course, are completely separate polypeptide chains, and their backbones are not connected. Domains, however, are extensions to the peptide's backbone, making them very different terms, and it's important to point that out now to ensure proper understanding.

We'll revisit the term subunits when we get to quaternary structure later in our course. Another very important thing to note about domains is that they are often grouped according to the structural and functional characteristics they exhibit. Scientists can learn a lot from domains. For example, if a scientist discovers a brand new protein and within this protein, recognizes a particular domain that they have studied in another protein, this could reveal some of the functions of the new protein. That's why it's critical to study a protein's domains.

In our example below, we will circle the three most obvious domains in the figure. This figure represents one single polypeptide chain that is completely folded. We've colored the different domains to make them easy to identify. You will see that we have one domain in the back in purple, another domain in the middle in green, and the last domain in blue. Even though this is a single polypeptide chain, it has these independently folding units. If you were to cut off, for example, the purple section from the rest of the chain, this section, because it's its own domain, would still be expected to fold properly. The same applies to all the other domains here. These are the three domains.

This concludes our lesson on protein motifs and domains, and we'll be able to get some practice in our practice video. I'll see you guys there.

Which of the following statements concerning a Cas9 endonuclease's protein domains is true?

• A. They are a form of its secondary structure.
• B. They have only been found in eukaryotic proteins.
• C. All its domains consist of separate polypeptide subunits.
• D. They retain their shape when separated from the protein.

Which of the following is true concerning the motifs and domains of proteins?

• A. Many domains make up a motif.
• B. Every polypeptide chain is limited to one domain.
• C. Separate proteins with similar domains are likely to have a similar function.
• D. All domains of a protein have the same function.

Appropriately label the domains of the membrane embedded protein in the figure below.

So this practice problem wants us to appropriately label the domains of the membrane-embedded protein in the figure below. Notice that inside the figure, what we have is a phospholipid bilayer. We've got this yellow region here, which is the hydrophobic region of the membrane. Notice that because of the curvature of this phospholipid membrane, the way that it’s curving, we can see that over here on the outside, this must be the outside of the cell and that must mean that on this side, this must be the inside of the cell. Our first option here says the transmembrane domain. The transmembrane domain is literally the domain or portion of the protein that’s going to be traversing the membrane. That’s referring to this entire region right in here. So, this would be option A, and that's the transmembrane domain. Next, we have is the cytoplasmic domain, and the cytoplasmic domain is going to be the portion of the protein that's on the cytoplasmic side, and remember, the cytoplasmic side is the inside of the cell. That's referring to this domain, this region of the protein over here. So that would be B here for the cytoplasmic domain. And then, of course, our last domain is going to be the extracellular domain, which is going to be on the outside of the cell right up here in this region. And so that is going to be C here for the extracellular domain. A single protein, which is embedded in a membrane, can have these three different domains, and each domain could have its own unique function. Again, each domain is important to keep that in mind as we move along throughout our entire course. So, this concludes this practice, and I'll see you guys in our next one.

The structure of an immunoglobulin G (antibody) molecule is shown schematically below. The black solid lines depict individual polypeptides and so there are four polypeptides in the quaternary structure of this molecule. Each of the spheres represents a stretch of about 100 amino acids folded independently of the rest of the polypeptide and performs a specific function in the molecule. Therefore, each sphere was given its own individual name (VH, CH1, CH2, etc.). Without knowing any additional details, you can predict that there must be TWELVE ___________________ in this molecule.

• A. α-helices.
• B. Domains.
• C. Subunits.
• D. Motifs.

What is the main difference between an endonuclease's domains and its subunits?

• A. Its domains are composed mostly of the α-helix, while subunits contain both α-helices and β-sheets.
• B. Its subunits are separate polypeptide chains, while its domains constitute a part of a polypeptide chain.
• C. Its domains do not have secondary structure, whereas its subunits have do.
• D. Its domains are stabilized by hydrogen bonds, while its subunits are stabilized by disulfide bonds.

Here’s what students ask on this topic:

What are protein motifs and how do they function in proteins?

Protein motifs, also known as super secondary structures, are specific patterns and combinations of secondary structures like alpha helices, beta strands, beta turns, and loops. These motifs serve various functions in proteins, such as providing structural strength and creating binding sites for different molecules. For example, the helix-loop-helix motif is involved in DNA binding, while the coiled-coil motif provides structural stability. There are several hundred known motifs, but common ones include the helix-loop-helix, coiled-coil, beta-alpha-beta, and hairpin motifs. Understanding these motifs helps in predicting the function of proteins based on their structural patterns.

What is the difference between protein motifs and protein domains?

Protein motifs are specific patterns of secondary structures like alpha helices and beta strands, while protein domains are larger, independently folding units composed of multiple motifs. Motifs are the building blocks that combine to form domains. Domains can fold independently from the rest of the protein and often have distinct functional and structural characteristics. Unlike motifs, domains can be found on a single polypeptide chain and are extensions of the peptide backbone. Understanding the difference is crucial for studying protein structure and function, as domains often indicate specific roles within the protein.

How do protein domains contribute to the overall function of a protein?

Protein domains are independently folding units within a protein that contribute to its overall function by providing specific structural and functional capabilities. Each domain can perform a distinct role, such as binding to other molecules, catalyzing reactions, or providing structural stability. Because domains can fold independently, they can be modular, meaning they can be found in different proteins with similar functions. This modularity allows scientists to predict the function of unknown proteins by identifying known domains within them. Domains are critical for the versatility and functionality of proteins in various biological processes.

What are some common types of protein motifs and their functions?

Some common types of protein motifs include the helix-loop-helix, coiled-coil, beta-alpha-beta, and hairpin motifs. The helix-loop-helix motif consists of two alpha helices connected by a loop and is often involved in DNA binding. The coiled-coil motif consists of two alpha helices wound around each other, providing structural strength. The beta-alpha-beta motif consists of a beta strand connected to an alpha helix, which is then connected to another beta strand, often involved in enzyme active sites. The hairpin motif consists of two anti-parallel beta strands connected by a loop, commonly found in beta sheets. These motifs play crucial roles in the structural and functional aspects of proteins.

Why is it important to study protein motifs and domains?

Studying protein motifs and domains is important because they are fundamental to understanding protein structure and function. Motifs are specific patterns of secondary structures that contribute to the protein's overall shape and function, while domains are larger, independently folding units that can perform distinct roles. By recognizing these structures, scientists can predict the functions of unknown proteins, understand how proteins interact with other molecules, and design drugs that target specific protein regions. Additionally, studying motifs and domains helps in understanding evolutionary relationships between proteins and can provide insights into the mechanisms of diseases caused by protein misfolding or mutations.