Protein Degradation

Hi in this topic, we're gonna be talking about protein degradation. So one of the main ways that proteins are degraded is through what we call the ubiquitous protease own pathway. And so what is the proteas own? The protease um is actually a multi subunit protein complex that is able to degrade proteins. So how does this happen? Well, proteins must be labeled with another protein called ubiquity in and if proteins are labeled with the ubiquity in that targets them to the proteus zone for degradation. So what is ubiquitous in? It's about 76 amino acid protein. It's found in all eukaryotic organisms. And in order to degrade proteins, proteins need to be labeled with at least one called mono ubiquity intonation or two or more than one which is polly ubiquity in proteins. So this pathway occurs in five steps. So get ready to write down these steps and sort of learn these steps um and requires energy from a Tv. So let's go through these steps together. First is ubiquitous is activated by an E. One. Ubiquity inactivation enzyme. So in our image here you can see E one and here's ubiquity in and it becomes activated. So this is the activation to form this complex. Then in step two, the activated ubiquity and then binds the E two ubiquity dating conjugating enzyme. So here we see this process happening. So this is step one and this is step two and finally after step two, you end up with E two bound to ubiquitous. Then for steps 3 4 and five let me disappear. Then the E. Too complex. So we're gonna start here. So this is our starting point. So the E two um complex with the ubiquity is attached onto the E three is attached onto the target protein via the E. Three ubiquity in line case. And so we can see this here. So we have our E. Two and ubiquity in the E three comes in and attaches it to the protein that needs to be ubiquitous nated. Now there is an important thing to realize about the E. Three protein and that each E three recognizes a different substrate protein. So there's a ton of E. Three proteins, each recognizing different a different protein for ubiquity nation. So E three is responsible for selecting the protein that needs to be degraded. So this is gonna be step three. Now, once this complex is formed the it can become ubiquitous nated substrate becomes ubiquitous mated. And then the ubiquitous native protein can be recognized by the protea is um And so you can see that this step can happen multiple times with multiple coordination. And then once this happens this is going to be step four. And the proteus zone recognizes it. And then step five is the protein is unfolded and fed through the protea zone which is actually cylindrical and the protozoan contains 80 dependent 80 P dependent protein basis which are enzymes that chop up proteins into short peptides. And so the entire protein remains bound to the proteins. Um until it's entirely chopped up. So what does the party zone look like? So in step five remember that it gets the protein is unfolded and fed through. So you can imagine there's this big complicated protein here. It's been labeled with ubiquity means you be and it gets targeted to the protea zone and it gets fed through this channel and a single sort of unfolded polyp peptide chain. Um And inside this channel is where the protein is bound and chopped into short peptides. So that is the ubiquity in protease own pathway of protein degradation. Now let's move on.

okay in this video, we're gonna be talking about the license zonal pathway, which is another way that proteins are degraded in the south. So the license home is a really important organ l because it can degrade proteins and it does this because the lumen in the license zone where the inside of the license zone contains enzymes known as protein cases, which are responsible for chopping up proteins. And so there's this process called atop A. G. Um and it's kind of a process of cell death or cell destruction. You may have heard of it before cell eating. Um but all of these processes involved a lot of protein destruction and this protein destruction happens via license OEMs and Khafaji. And you don't necessarily need to know much about ontology right now, but we will talk about it in future topics. Um and just sort of know that atop A G. The license alone is responsible for these kind of overarching approaching degradation pathways like atop A. G. And then the license only pathway is kind of special in a way because it can really rapidly respond to nutrient, it's an external signal. So proteins that are degraded by the licensing will pathway don't need to be labeled, they just need to get into the license zone, which can happen really quickly. So if we're looking at the license only protein degradation here, we have a license zone. This is gonna be the lumen of the license zone, the internal part of the license zone and we have a polyp peptide chain here and it is bound to some type of proteus which is responsible for breaking it up into its free amino acids and degrading the protein. So now that's the license animal protein degradation pathway. So now let's move on.

So in this video we're gonna talk about protein degradation regulation. So protein degradation in and of itself actually can regulate the amount of protein in the cell at a certain time. Because if we degrade the protein then it can no longer do its function. So it's kind of degradation is a form of protein regulation. So there are really two reasons that protein needs to be regulated via degradation. The first is that proteins have lifespans and those lifespans can vary from seconds, two decades. But eventually when the protein runs through its lifespan, it needs to be degraded. And so if it isn't, that means that there aren't proper protein levels that and the protein levels are crucial for certain chemical reactions to occur. So if you have too much protein or too little protein, the chemical reaction won't occur and that it would be devastating. So how does a protein get degraded when its lifespan is up? I mean, it's not that it just turns 80 and um it's heart fails because that doesn't make any sense for a protein. So what happens for protein is usually a protein contains something like an interminable degradation signal and this degradation signal is hidden until it's time to be degraded and then when it's time to be degraded, something happens in the cell which triggers the release of the signal and then something like ubiquity in for instance, combine this region and targeted for degradation. Now, a second reason for regulation is that proteins occasionally misfold and that can be devastating to the cell when they do this. And so abnormally folded proteins are misfolded, proteins can actually aggregate in the cell and cause disease, which we obviously don't want. So we need proteins to be able to degrade over time, either when they're misfolded or when their time is up so that they don't wreak havoc in the cell. So um how this would happen for the protein lifespan is, for instance, some type of confirmation all change. So you have this one protein here. A confirmation I'll change occurs here, which changes the confirmation but also releases an internal degradation signal which before was hidden and now is released and then ubiquitous in combined. And that can target the protein for degradation when its lifespan is up. So now let's move on.

Which of the following is not associated with protein degradation?

• A. Ubiquitin-proteasome pathway
• B. Lysosomal pathway
• C. 5' Cap
• D. N-terminal degradation signal

Which protein is responsible for attaching a ubiquitin molecule onto a protein to target it for degradation?

• A. E1 ubiquitin activation enzyme
• B. E2 ubiquitin conjugating enzyme
• C. E3 ubiquitin ligase
• D. E4 ubiquitin attachase

Before entering the proteasome the protein marked for degradation is unfolded.

• A. True
• B. False

What is the name of the signal released by some proteins when they can be degraded?

• A. Ubiquitin binding signal
• B. N-terminal degradation signal
• C. C-terminal degradation signal
• D. Proteosome signal