Protein Basics - Online Tutor, Practice Problems & Exam Prep

Proteins are composed of polypeptide chains formed by linking amino acids through peptide bonds. Each amino acid has a unique R group that determines its properties, influencing protein structure and function. Proteins can be monomeric (single chain) or multimeric (multiple chains). Folding is guided by the amino acid properties and is restricted by the polypeptide backbone and Gibbs free energy, leading to a native conformation. Chaperone proteins assist in proper folding, crucial for preventing diseases related to misfolded proteins. Understanding these concepts is essential for studying biochemistry and molecular biology.

Protein Structures

Hi. In this topic, we're going to be talking about protein basics. So the first basics that we need to know are just some basic vocabulary, so that when we start talking more about complex protein issues, we understand what we're talking about. So, first, we're going to talk about protein structures. And, proteins are made, or, you know, form these structures, by linking amino acids together. So, the thing that, or a polypeptide chain is formed by peptide bonds between amino acids. So, when a bunch of amino acids are linked together, we actually call that a polypeptide chain.

Now, how does a polypeptide chain connect with what a protein is? Well, a multimeric protein is going to have multiple polypeptide chains. Each one is going to be called a subunit. And then a monomeric protein is made up of a single polypeptide chain. So if a protein only contains 1 polypeptide chain, that's a monomeric protein. If it contains multiple polypeptide chains, then it's a multimeric protein, and each one of those chains are called a subunit.

So, the polypeptide chain is made from a polypeptide backbone, which has a repeating sequence of nitrogen and carbon atoms. So, you can see this here in this example down here. Let me go away while we talk about this. So, if we were to follow this, we have carbon, nitrogen, carbon, nitrogen, carbon, nitrogen. So these repeating sequence of nitrogen and carbons. Now, the N-terminus here is going to be the side with the amino group or the NH3+ group at its end. The other end has a C-terminus, which has a carboxyl group at its end. So if we're looking at this, this is a 3 amino acid polypeptide chain. We have 1, 2, 3 amino acids. And here, we have a carboxyl group, COOH, and here we have NH3+ right here. And so this is going to be the N-terminus and this one's going to be the C-terminus. And so those are the components that make up the basics of a polypeptide chain. So now, let's move on.

Amino Acids

So now let's talk about the amino acids themselves. Polypeptide chains are made by linking amino acids together. Each amino acid has unique properties. All amino acids have a carboxyl group, an amino group, and a hydrogen around this sort of central carbon. There is a property called an R group, which is a side chain on the amino acid, and that differs between amino acids and gives them the unique properties that I have talked about. This R group can be polar and charged, which allows for it to form ionic bonds with other charged molecules. It can be polar and uncharged, which can form hydrogen bonds with other molecules, including water. It can be non-polar, making the overall protein unable to interact with water. And then there's a final group called the other group, which consists of amino acids that don't necessarily fall into any of these other categories. These groups classify the different types of R groups that they are. You can see how these differences in the amino acids give the overall polypeptide chain or protein unique properties based on how many of which kind of R groups are present.

Another property that we've talked about before, but I just want to mention again, is that amino acids exist as stereoisomers. The four groups are asymmetrically arranged around the alpha carbon. These are called the D and L forms. But, since we're talking about proteins, just know that only the L form is used in proteins.

The first example that we are going to talk about here is the structure of an amino acid. We have our alpha carbon here, our amino group, our carboxyl, our hydrogen, and our R group. Remember, this is the one that gives it the unique properties.

The second example here is going to be the 20 amino acid structures. Some of you are going to have to memorize all 20 of these. Some of you will have the option of memorizing all 20 of these for a test. For instance, when I took cell biology, I had to memorize all of these for extra credit on a test. There's not really much I can help you with other than showing you all the structures here, and that's just going to be a major factor of getting some flashcards out and trying to memorize these structures. The amino acids I am presenting here are organized by the R group and by the properties that they have. This one up here has charged side chains, these are going to be polar uncharged, and these are the three special cases, the others. And then these ones down here have hydrophobic or are non-polar. Here are the 20 amino acids, for your use in case you decide that you either need to or just want to learn all of these structures. I will say, if you're planning on taking biochemistry, knowing them now is going to be really useful in the future. If you feel like maybe you should go ahead and do it, feel free.

With that, let's now move on.

Protein Folding

Okay. So now, let's talk about some larger protein folding concepts that you need to know. Proteins form into complex shapes. There are so many different proteins, and they all have different functions. So, of course, they all have to have a different shape. Some proteins, or most of them, can actually self-assemble. Their amino acids give them certain properties, and those properties allow for folding without assistance. Like I said, the information required is just inherent in the amino acid side chains of the R groups.

There are a couple of terms here that we can use to talk about what state the protein is in. One is denatured, which is when it's in its unfolded state. The self-assembling proteins will renature or reform when in proper conditions. Now, can they just fold anywhere into any shape, willy-nilly, whatever they want? No. And, that's because the peptide bonds in the polypeptide backbone restrict movement. This is a limit on protein folding. The polypeptide backbone is restrictive. It has certain bonds that only allow for so much movement. This really prevents proteins from folding into just any shape they feel like, and it helps the protein to form its correct shape.

Here's an example of what a denatured protein would look like: here, it's in its proper form, and here, it's denatured. This took heat, for instance, to denature it. Lots of things can denature, unfold proteins, including pH and heat. But, self-assembling proteins can take it upon themselves to sort of go back to their folded form whenever they are in the proper conditions. We call conformation its folded shape, and it folds due to the properties of the R group. Now, like I've already said, it can't necessarily fold into whatever shape it wants to. Instead, it is restricted by the polypeptide backbone, but it is also restricted by Gibbs free energy. The conformation that it forms is the one with the lowest Gibbs free energy because it doesn't want to expend energy to fold. Therefore, there are tons of conformations proteins can form, but the one with the lowest Gibbs free energy is usually the one that it does form, and this is called a native state. Usually, there is a small number of conformations with kind of equal Gibbs free energy, and that's the state that the protein will actually form in. And, of course, there are thousands of possibilities of what this could be, but the native state is generally the one with the lowest free energy.

The conformation, the folded shape, is mainly formed through non-covalent interactions. We've talked about some of these in other videos. These include things like hydrogen bonds, ionic bonds, van der Waals forces, and hydrophobic interactions. The protein conformation is held in its complex shape based on non-covalent interactions. But there is a form of covalent interaction called a disulfide bond, which can form between sulfur atoms on two cysteine amino acids. This is a stabilizing bond that is very important in protein conformation. Mostly, the protein folds using non-covalent bonds but can use this covalent disulfide bond if needed. So here we have just a protein, and you can see here it’s folded into this complex shape. And, all these little things sticking off here, we can refer to as amino acids, and all of them have R groups that have different properties that allow the protein to form into this conformation versus any of the others that it could have folded into.

Sometimes, the protein can’t fold on its own. When that happens, it requires the use of proteins called chaperone proteins. There are two groups. The first is called molecular chaperones, and they are responsible for stabilizing unfolded or partially folded proteins. They do this by binding to the protein and preventing the aggregation of the unfolded or misfolded proteins. One that you may read about in the book is HSP70. By preventing this aggregation, it allows the protein to have a little more time to fold correctly. The second group is chaperonins, and chaperonins work differently because instead of just binding to the protein, they create small chambers within the cell that allow for the sequestering or separation of unfolded proteins from water or other molecules that may be present in the cytosol. These form cylindrical folding cores, and the unfolded protein sits in there, separated from the environment. Entrance into the chaperonin core is controlled through proteins that act as lids that open and shut when the protein needs to enter and shut while it’s in there. It refolds, and then it can open again and let it out. An example of this you might see in your book is HSP60. Chaperones can refold proteins. Generally, these require energy through ATP hydrolysis. They are not energy efficient; they require energy to function. Often, these do not necessarily work as they should in diseases like Parkinson’s and Alzheimer’s, which are really diseases of misfolded proteins. So this is what a chaperonin looks like. You can see there’s a nice hole where the unfolded protein goes into to refold. And here you can see it from another angle with the chamber inside of there. Normally, there would be some kind of lid here that could open and close, allowing proteins in and out as necessary. So, that’s protein folding. We've shown the basics of protein folding. Let's now move on.

Four Protein Models

Okay. So now we're going to talk about the 4 protein models. You're going to see proteins shown in many different ways by your professor, and also in textbooks that you may have. There are 4 different ways of presenting, and this is kind of the overall organization of the polypeptide chain. The second one is the ribbon model, which shows the polypeptide backbone folding. The wire model is going to show the amino acid side chains. And the space filling model is going to show a contour map of the protein surface. So, let's look at the example, and we'll go over which one is which.

The first thing you see here is your backbone model. You can see this is the overall organization of the polypeptide backbone. Then you have the ribbon model here, which has the polypeptide backbone, but also its orientation. You have this orientation here. We're going to talk about what that is. You have a different orientation here. And so, this is the polypeptide backbone, just the same as in the backbone model, but you can see that they're showing different things. Now, the wire model is here, and you can see that we started adding in amino acid side chains here. You can see some here. There are usually amino acid side chains wherever these yellow things appear. And so, we're getting more complex as to what this protein actually looks like. And then, finally, you have this space filling model. Scroll down a little. That's the contour map. And, you can see the surface of the protein, where the divots are, where there are raised atoms, and follow this along in creating this contour map of what the overall protein shape is. So those are the 4 models that you're going to see of proteins in your textbook or in lecture. So let's move on.

Which of the following is false about the R group of amino acids?

• A. They give polypeptide chains unique properties
• B. They assist in forming complex protein structures
• C. They control the stereoisomer form of the amino acid
• D. They can be nonpolar

A protein C-terminus is named that way because it contains what molecule?

• A. An extra carbon
• B. A COOH group
• C. A CH₃ group
• D. A Chloride

A protein's conformation is formed through all but which of the following?

• A. Hydrophobic Interactions
• B. Disulfide bonds
• C. Covalent bonds between carbons
• D. Noncovalent bonds between R groups

Which of the following protein models would you use if you wanted to gain an idea of what the surface of a protein looked like?

• A. Backbone
• B. Ribbon
• C. Wire
• D. Space-Filing

Here’s what students ask on this topic:

What are the four levels of protein structure?

The four levels of protein structure are primary, secondary, tertiary, and quaternary. The primary structure is the sequence of amino acids in a polypeptide chain. The secondary structure refers to local folded structures that form within a polypeptide due to interactions between atoms of the backbone, such as α-helices and β-pleated sheets. The tertiary structure is the overall three-dimensional shape of a single polypeptide chain, stabilized by interactions between R groups. The quaternary structure is the arrangement of multiple polypeptide chains (subunits) in a multimeric protein.

What is the role of chaperone proteins in protein folding?

Chaperone proteins assist in the proper folding of other proteins. They prevent aggregation of unfolded or misfolded proteins and help them achieve their correct conformation. There are two main types: molecular chaperones, which stabilize unfolded proteins, and chaperonins, which provide a secluded environment for folding. Chaperones often require ATP to function and are crucial in preventing diseases related to protein misfolding, such as Parkinson's and Alzheimer's.

How do amino acid R groups influence protein structure?

Amino acid R groups, or side chains, determine the unique properties of each amino acid, influencing protein structure and function. R groups can be polar, nonpolar, charged, or special cases, affecting how amino acids interact with each other and the environment. These interactions, including hydrogen bonds, ionic bonds, van der Waals forces, and hydrophobic interactions, guide the folding and stability of the protein, ultimately determining its three-dimensional conformation.

What is the difference between monomeric and multimeric proteins?

Monomeric proteins consist of a single polypeptide chain, while multimeric proteins are composed of multiple polypeptide chains, each called a subunit. The subunits in multimeric proteins can be identical or different and are held together by non-covalent interactions or disulfide bonds. The arrangement and interaction of these subunits contribute to the protein's overall structure and function.

What are the different models used to represent protein structures?

There are four main models used to represent protein structures: the backbone model, ribbon model, wire model, and space-filling model. The backbone model shows the overall organization of the polypeptide chain. The ribbon model illustrates the folding of the polypeptide backbone. The wire model includes the amino acid side chains, providing more detail. The space-filling model displays a contour map of the protein surface, showing the spatial arrangement of atoms.