So now that we've covered the basics of protein folding, in this video we're going to talk about how proteins fold within a cellular environment using chaperone proteins. Some small proteins are able to quickly fold up into their native proper shapes without any outside intervention whatsoever. However, typically, large proteins fold very slowly and because they fold slowly, they are more likely to need help folding faster. Why is it important that proteins fold fast? It turns out that within a cellular environment, it's overcrowded with lots and lots of molecules. The slower that a protein folds, the more likely it is going to interact with a molecule that will disrupt and interfere with the proper protein folding process, which will lead to misfolded proteins. Misfolded and unfolded proteins can result in protein aggregates, which are just clumps of proteins. However, the protein aggregates are nonfunctional proteins, which means they will not perform their normal job. Many different diseases, such as Alzheimer's and Parkinson's, result from misfolded proteins called prions. It's in the cell's best interest to make sure that all of its proteins fold fast to prevent prions and diseases. That's exactly where chaperone proteins come into play. Chaperones are actually proteins themselves that physically bind to other unfolded proteins and use ATP or energy to increase the rate of correct folding. By rate, we mean the speed of the folding. They do this by physically binding to other unfolded proteins and preventing other molecules from interfering and disrupting the proper protein folding process. An example of chaperones are heat shock chaperones, which facilitate proper folding of proteins denatured due to pretty much any type of cellular stress, including heat. Heat shock chaperones are actually misleadingly named because they were called heat shock chaperones because they were discovered while heat shocking cells. However, heat shock chaperones are actually involved in helping proteins fold that were denatured due to any type of cellular stress including changes in pH, decreases in temperature, increases in temperature, or even UV radiation. A specific class of chaperones are chaperonins. Chaperonins are a class of chaperone that also use ATP or energy to assist in proper protein folding, but they specifically do that by creating a cage around the protein, the unfolded protein. This creates a very nice environment where the unfolded protein can fold properly without any interference from other molecules.
Let's take a look at our example below to compare molecular chaperones and chaperonins. On the left, we have chaperones, and on the right, we have chaperonins. Starting with the chaperones on the left, we know that when a protein is first produced, it is produced as an unfolded protein. This orange squiggly line that we see here is an unfolded protein, and it could be that this unfolded protein results from denaturation due to lots of different types of stresses. You could imagine that it could be due to heat, for instance. However, sometimes this path is slow and folding is slow, especially interfere with the proper protein folding process and that will lead to misfolding of the protein. Over here, what we have is a misfolded protein. We know from our lesson above that misfolded proteins are at risk of protein aggregation, where they can form clumps of proteins that are nonfunctional. We know that prions are the names of protein aggregates that cause diseases such as Alzheimer's and Parkinson's. It's in the cell's best interest to avoid this pathway, because this pathway will lead to disease. One of the ways that cells can avoid this pathway is by using chaperone proteins. Chaperone proteins physically bind to the unfolded protein and prevent other molecules from interfering with the protein folding process. They use ATP or energy to increase the rate of the proper protein folding to generate the native protein shape faster without having to worry about misfolded proteins. Through this process, we're able to get to the native protein shape faster without having to worry about misfolded proteins. However, what you'll also notice is that some chaperones are capable of interacting with misfolded proteins and refolding them back into their native shape. Chaperones can influence multiple different areas within this diagram, which is a helpful thing to again, avoid this aggregation and avoid disease. Later in our course, we'll talk about another method that cells can use to avoid aggregation, which is to mark misfolded proteins for degradation, so that they essentially chop down the protein into protein fragments that are not harmful. This is not a process that chaperones are involved with. We'll talk more about degradation later in our course, so something to look forward to.
On the right, we have chaperonins, a specific class of chaperones that essentially isolate unfolded proteins into a cage. Essentially, our unfolded protein is embedded into a cage-like area, where it's secluded and no other molecules are able to enter to interfere and disrupt the process. Essentially, it uses energy, just like chaperones do. The only thing is that it creates this cage that uniquely identifies it as a chaperonin. Moving forward in our next couple of practice videos, we'll be able to get practice with the concepts of chaperones and chaperonins, so I'll see you guys in those videos.
