G protein-Coupled Receptors - Video Tutorials & Practice Problems
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G protein-Coupled Receptors
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in this video, we're going to begin our lesson on G protein coupled receptors. And so already in our previous lesson videos, we briefly introduced G protein coupled receptors, And so from those older videos, we know already that G protein coupled receptors are commonly referred to as just GPC ours for short. And so we could go ahead and put GPC are here in this blank. Now these g protein coupled receptors, or GPC ours, as their name implies with the receptor right here are really just receptors themselves. But more specifically, these are receptors that will associate themselves or couple themselves with what's known as a G protein. Now we'll introduce exactly what a G protein is a little bit later in this video. But for now, bear with me here that the G protein coupled receptors are just receptors themselves that associate or couple themselves with something called a G protein. Now the G protein coupled receptor, or GPC, are because it is a receptor itself. Of course, we know that it is an integral membrane protein, but more specifically thes GPC. Ours are integral membrane proteins that consist of seven trans membrane Alfa Healy sees or seven trans membrane segments or TMS for short. And so sometimes you'll see that these G p C. R s are referred to as seven TMS proteins because again they have these seven trans membrane Alfa Hillis ease. And so, if we take a look at our images down below over here on the left hand side, notice that we're showing you three different representation of a g p c r. Notice that we're showing you one up here. We're showing you another right here, and we're showing you our third down below. And so we'll explain this here very short. Now, the top left representation of the GPC are clearly you can see that the G PCR has these seven trans membrane Alfa. He'll ISI is right here and recall that the Alfa Healy sees can actually sometimes be abbreviated as these cylinders that you see right here and so you can see that we've colored these seven trans membrane Alfa Ulysses different colors just to help you guys distinguish them a little bit easier. And so again, because GP CRS have seven trans membrane Alfa Hillis ease, they're sometimes called seven TMS proteins. Now what's also important to note about these g p c R s is that they actually have an extra cellular end terminal and an interest cellular C terminal. And so, if you take a look down below at this same representation right here, what you'll notice is that the outside of the cell is this blue background up above and the inside of the cell is this yellow background down below. And so, of course, we know that the extra cellular space is going to contain the end terminal domain and so we could go ahead and fill in the end terminal here to remind us that is going to be on the extra cellular side on the outside of the south. And of course, the intracellular side, the inside of the cell is going to contain the C terminal domain of this GPC are protein. And so this is another important feature that you guys need to know about the G p. C. R. S. And so this representation at the top left is very important because again, it highlights these features that you guys need to know. It shows the seven trans membrane alfa he'll seize. It shows the N terminal outside in the C terminal inside. But really, this GPC our representation right here is not the best or the most realistic representation of a g p c. R. Because really, these seven trans membrane Alfa Hillis these are not perfectly aligned side by side like this In real life, there actually completely overlapped with each other like what you see over here. And so this GPC our representation is showing the same GPC are is this over here? Except it's showing, um, or realistic version where the seven trans membrane alfa jealousies are overlapping with each other. But still the N terminal is outside and the C terminal is inside now down below. What we have is our third representation of the GPC are and really this representation that you see down below is the representation that we're going to use here. A clutch prep to symbolize the GPC are. And that's because it's a more simplified, clean looking version. And later, once things start getting more and more complicated, you're going to appreciate having a more simplified version here. But just because we're using this more simplified version of the GPC are moving forward in our course does not mean that you cannot forget about these important features of the GPC are again having seven trans membrane alfa. He'll sees an end terminal that is extra cellular in a C terminal that is intracellular. Now, in our third representation of the GPC are down below. Which will notice is that the GPC are here in the tan color is actually associated with or coupled with this green structure down below, which is our G protein, and so that transitions us perfectly into the G proteins. So the G proteins are called G proteins because really, they're GTP binding proteins, and so these are intracellular lipid linked proteins that can hide relies as their name implies, G T p. And so not only do they hide relies GTP into G d. P, but the's G proteins, specifically the ones that are associated with the G protein coupled receptors, have three different sub units that air termed the Alfa the beta and the gamma sub units. And so if we take a look at our image down below, notice that the green structures here are showing our G protein and notice that it has the gamma, the beta and the interactive one right here. The Alfa sub unit and really the Alfa sub unit is going to be the one that is most important for us to know as we'll see when we move forward in our course. And that's why it's the one that is interactive here now, because there are three different sub units in this G protein, it is known as a hetero try. Merrick G protein hetero meaning different because there are three different sub units. The try of course in here means three and America is referring to the sub units. So this is a hetero try, Merrick G protein. Now there are other types of G proteins that air, not hetero. Try Merrick and moving forward in our course, we're actually going to see some examples of G proteins that are not hetero. Try Merrick. So that's important to keep in mind here. But the G proteins that we're talking about that are associated with the GP CRS. They are hetero. Try Merrick G proteins. Now, what in the world is this GTP here that we were talking about, that these G proteins actually hydrolyzed Well, GTP stands for guana seen triphosphate and so you can see the GTP embedded in here. And so GTP really serves a similar type of function to a Dina seen triphosphate or a teepee. And so, of course, we know all about 80 p and so down below, over here. And our image on the right hand side here, which will notice, is that we're showing you a teepee hydraulic assist on the top image and down below. What we're showing you is GTP, hydraulics, ISS in the bottom image. And so what you'll notice is that 80 p we know is the high energy molecule and eso is GTP and so you can see that we have these little yellow backgrounds behind these to represent that they are high, high energy. And so when the G protein is bound to the GTP version, that means that it's going to be in its active state. And of course, when GTP is hydrolyzed down to G d. P, we know that it's going to be the inactive form or the low energy form. Just like we know that a D. P is the low energy form of a teepee. And so really you can think a t P and G T p r both the high energy active form, whereas a. D p and G d p r the low energy inactive forms and so you can see that hydraulics ISS is going to remove a phosphate group. And so really, the g protein that we see here as we mentioned up above eyes capable of hydra allies ing the GTP. So when we say GTP, hydraulics is moving forward. What we really mean is this reaction right here taking the GTP and hide relies ing it which of course, is going to utilize water. Since hydraulics ISS, we know has the hydro prefix in it. It will hide, relies it so that the fox one of the phosphates is removed and it becomes a g d p molecule. Now you can see really the difference between GDP and A T. P is the nitrogenous base here that is attached and so comparing the differences here you can see that is really what distinguishes uh 80 p from GTP. But other than that, they're structures are incredibly similar. And so hopefully by just keeping in mind that the GTP is very similar in function to a teepee, Then you guys will be good now. One thing to note is that over here on the left hand side, notice that RG protein is bound to G. D. P. It's bound to the low energy inactive form. And so what that means is that this hetero try, Merrick G protein must be in the inactive form, since it's bound again to G. D. P. And so this is exactly how the G protein starts in the beginning of our G protein coupled receptor pathway. And so this is a perfect transition to our next video. And so this year concludes our introduction to the G protein coupled receptors. And again we'll talk more and more about these as we move forward in our course and I'll see you guys in our next video.
2
concept
G protein-Coupled Receptors
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8m
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in this video, we're going to talk about the three essential components of GPC our signal transaction pathways and you could see that we have these three essential components number down below. Now, as we move forward in our course and talk about very specific GPC, our signal transaction pathways, we'll see that there are ah lot mawr than just three components involved in those pathways. But really, the three components that we're going to talk about here in this video are the ones that we'll see are the most consistent across the different GPC, our signal transaction pathways that we're going to talk about in our course. And so that being said, Let's get started with number one here are first essential component. And that is of course, the GPC are itself or the G protein coupled receptor itself, which, of course, we already know is a trans membrane receptor that will actually undergo a confirmation. Will change upon ligand binding, and ultimately this confirmation will change is going to activate the G protein that we know the GPC are is associated with and so down below in our image noticed that we're showing our first essential component the GPC are here as this tan structure and so we could go ahead and fill in. The GPC are right here in our image and, of course, upon lie again binding. So when the lie again actually binds to our GPC are noticed that it actually undergoes a confirmation Allchin change as we see here in our image. So now, of course, we know that this GPC are undergoes a confirmation will change in order to activate the G protein. And that leads us to our second essential component, which is the G protein itself. And so recall that the G protein is an interest cellular lipid linked peripheral membrane protein that actually can bind to GDP and GTP. And so it will actually replace G d p, the low energy inactive form with G T. P, the high energy active form when it's actually activated. Which makes sense since, of course, GTP is the active version. And so when the G proteins activated, it will bind GTP and the G protein we know has the ability to hide, relies the GTP, and so it will actually slowly hide relies the GTP. Now again, we know that the G proteins that we're talking about here in this context contained three different sub units and Alfa sub Unit, a beta sub unit and a gamma sub unit. And these sub units will actually disassociate toe form an Alfa sub unit and a beta Gamma sub unit upon GTP binding. And so essentially, the Alfa sub unit is dissociating away from the Beta Gamma sub units. And so if we take a look at our image down below uh, notice over here in green, What we have is our g protein, our hetero try Merrick G protein. Since it has three different sub units which we know are the Alfa sub unit over here, the Beta sub unit and the Gamma sub unit. And so notice that here we're showing that it is bound to the G d P molecule, the low energy inactive form. But of course, upon binding of the lie again, once the lie again binds, it causes a confirmation. Will change in the GPC are and that confirmation will change in the GPC are ultimately causes GTP to replace the g d p and so down below Here we can say that upon ligand binding again GTP is going to replace the low energy G. D. P. And so if it's if GTP is binding, the high energy active form that is going to activate the G protein. And of course, as we said that the activated G protein is going to disassociate into the Alfa Sub unit and the Beta gamma subunits and so notice that the beta gamma subunits are here upon, like and binding. And of course, the Alfa sub unit is going to disassociate. And so we could go ahead and label this the Alfa Sub unit and notice that it is GTP bound now because it is. And it's high energy, active form. And so notice that this G protein Alfa sub unit right here and it's active form is actually now bound to this other structure that we see over here. And this is really the third component here of the GPC. Our signal transaction pathways and this is going to be the effect er enzyme, and so the affect er enzyme is another membrane bound protein, and more specifically, as its name implies, it is an enzyme, and so this is a membrane bound enzyme, and its job is to produce what's known as a secondary messenger upon activation by the Alfa G protein sub unit. And so ultimately, this Alfa G protein sub unit, which is active itself, is actually binding and activating this other, uh, membrane protein here that we're calling the defector enzyme. And again, the effect er enzyme is responsible for producing these secondary messenger that we can label down below. And the secondary messenger is actually going to be variable and different, uh, pathways that we cover moving forward. And so the secondary messenger's job a Z we'll see moving forward in our course is to affect downstream targets that ultimately lead to the cell response. And so, essentially what you end up getting is ah, lie again. Binds to the GPC are the GPC are undergoes. A confirmation will change that causes the G protein to exchange GTP with the GDP and so that causes the dissociation of the Alfa sub unit. And this dissociated Alfa sub unit activates the effect er enzyme here which goes on to produce a secondary messenger and the secondary messenger is ultimately what leads to the cell response and so you can see how a lie again on the extra cellular side can ultimately lead to a cell response within the sell through this signal transaction pathway. And we're going to be able to see very specific GPC our signal transaction pathways when we move forward in our course. But again, the three major components that you guys should be familiar with after this video are the GPC are the G protein and the effect er enzyme and how the effect er enzyme produces secondary messengers. And so this here concludes our introduction to these three essential components of GPC Our signal transaction pathways and as we move forward in our course, will be able to get some practice applying these concepts so I'll see you guys in our next video.
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Problem
Problem
A G protein-coupled receptor is comprised of ____ transmembrane α-helix/helices:
A
7.
B
8.
C
1.
D
10.
E
6.
F
14.
4
Problem
Problem
G protein-coupled receptors (GPCRs) are transmembrane proteins with ligand binding sites on the extracellular side of the membrane (near its N-terminal). What is the role of the G-protein in the GPCR signaling pathway?
A
G proteins phosphorylate GPCRs.
B
G proteins bind extracellular ligands and facilitate the transport into the cell.
C
G proteins activate enzymes that transduce the signal throughout the cell.
D
G proteins activate transcription of genes.
E
G proteins facilitate dimerization of receptor monomers.
5
concept
G protein-Coupled Receptors
Video duration:
4m
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So in our last lesson video, we mentioned that the role of the G protein is to activate the effect er enzyme. But really, that's only part of the full story. Because there are some G proteins that do activate the effect er, enzyme. But there are also other G proteins that inhibit the effect er, enzyme. And so here in this video, we're going to distinguish between the stimulatory and the inhibitory G proteins, or GS versus G. I. And so really, there are two types of G proteins that you guys should know that are classified according to their effect on the effect er enzyme. And so we have these two G proteins listed down below. And so the first one is going to be these stimulatory g protein. And so the stimulatory G protein is also known as G s, where the s here is for the S and stimulatory. And so these stimulatory G proteins, or GS, as their name implies, will stimulate or activate the effect er enzyme to create even mawr secondary messenger than normal and the second type of G protein, on the other hand, are referred to as inhibitory G proteins and these inhibitory G proteins are abbreviated as G I where of course, the I is for the I in inhibitory. And so these inhibitory G proteins, or G I, as their name implies, will inhibit or inactivate the effect or enzyme to create even less secondary messenger they in normal. And so, if we take a look at our image down below, over here on the left hand side, notice that we're saying that the stimulatory G protein G s is like the gas pedal in a car. And that's because the stimulatory G protein pretty much stimulates, activates or accelerates the production of secondary messenger just like the gas pedal in a car will accelerate the speed of a car. And, of course, the G I protein, the inhibitory g protein are like the brakes in a car. And so, just like the brakes in a car will slow down or decelerate the speed of the car. Thean hib it tore. E g proteins are going to decelerate. Slow down the production of secondary messenger and so notice Over here on the left hand side, we're showing you the Alfa sub unit of the G protein that has dissociated and is bound to GTP and notice that here it is actually activating the effect er, enzyme. And so because it's activating the effect of enzyme, we know that this is going to be the stimulatory g protein or G s, and then notice over here on the other side. What we have is another Alfa sub unit of a G protein, except notice that it has a red border here, but it's still going to be bound to GTP. Same exact thing still bound to GTP. However, this time, instead of activating the activated G protein here, bound to GTP, is actually going to inhibit the effect er enzyme. And so that means that this is going to be the inhibitory g protein, or G I. And so moving forward in our course, we're going to see examples of stimulatory G proteins or GS, and we'll also see examples of inhibitory G proteins or G I. And so this here is just an introduction to the stimulatory and inhibitory G proteins. But we will revisit this again as we move forward in our course. But for now, this concludes our introduction to the stimulus stimulatory and inhibitory G proteins, and I'll see you guys in our next video
6
Problem
Problem
Gi is the inhibitory G protein of various effector enzymes. If a toxin released from a bacterial infection enters cells & covalently modifies the α-subunit of Gi so that it can no longer bind GTP, which of the following is a likely result?
A
Increase in the synthesis of the secondary messenger molecule.
B
Decrease in the synthesis of the secondary messenger molecule.
C
The inhibitory G protein α-subunit will not dissociate from the β-γ subunits.