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Main content
Current time:0:00Total duration:12:48
AP.BIO:
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Video transcript

in this video we're going to talk about g-protein coupled receptors also known as GPCRs g-protein coupled receptors are only found in eukaryotes and they comprise of the largest known class of membrane receptors in fact humans have more than 1,000 known different types of GPCRs and each one is specific to a particular function they are a very unique membrane receptor and they are the target of around 30 to 50 percent of all modern medicinal drugs in fact the ligands that bind range from things like light-sensitive compounds to odors pheromones hormones and even neurotransmitters GPCRs can regulate the immune system growth our sense of smell taste visual behavioral and mood including things like serotonin and dopamine even now many G proteins and GPCRs still have unknown functions and is a topic heavily research in fact in just 2012 a Nobel Prize in Chemistry was awarded for research on GPCRs to start off let's talk a little bit about the structure of gpcrs it's impossible to really have a discussion about how gpcrs work without having an understanding of what they look like the most important characteristic of GPCRs is that they have seven transmembrane alpha helixes if we have this being our cell membrane and we have this being the extracellular side and this being the intracellular side if we have a GPCR a g-protein coupled receptor it'll span this membrane seven times so let's say it starts here and we go one two three four five six seven this is one of the most important characteristics of a GPCR they have seven transmembrane alpha helixes since this is such a unique and interesting structural characteristic we often also call GPCRs seven-transmembrane receptors so just to quickly label this is our ji pzr here as the name implies gpcr to interact with g-proteins they're coupled with g-proteins now it's important to talk a little bit about the structure of G proteins also G proteins in general are specialized proteins which have the ability to bind GTP and gdp in other words they are able to bind guanosine triphosphate and guanosine diphosphate hence the name g proteins now some g proteins are small proteins with the single subunit however when we talk about GPCRs all g proteins that associate with GPCRs are hetero trimeric meaning that they have 3 different subunits 3 sections so I'm going to go and draw this out the first section we call the alpha subunit the first subunit or section of this protein we call the alpha subunit the second we call beta and the third we call gamma so all three of these together the our alpha beta and gamma subunits together is our G protein you'll notice that I drew the alpha and gamma subunits with a little tail looking thing in our cell membrane and the reason why is because these are the two subunits our alpha and gamma which are attached to the cell membrane by what we call lipid anchors now the final thing about this picture that I need to draw in is our DP or gtp as you remember the whole point of a g-protein is because it binds gtp or GDP right now this protein is in active and so it binds GDP guanosine diphosphate this gdp binds to the alpha subunit when this protein becomes activated and we'll talk in just a second how that happens it will actually bind GTP instead so now that we've drawn out our actual picture of our g-protein let's talk a little bit about how our signaling pathway actually happens that's the whole point of membrane receptors is that they respond to signaling and ligands and they respond to the environment so as we mentioned before g-protein coupled receptors interact with a wide variety of molecules on the outer surface of cells each receptor binds to usually one or just a few very specific molecules fitting together like a lock-and-key so if we pretend that our signaling molecule is a circle like this the shape in which it should bind to the gpcr should be complimentary when this green signaling molecule binds to our gpcr our gpcr will actually undergo what we call a conformational change that shape of this GPCR will change which in turn triggers a complex chain of events which will ultimately influence different cell functions so as we mentioned our first step here is of course the ligand the signaling molecule has to bind to our gpcr once this ligand binds our GPCR is going to undergo a conformational change let's just go ahead and redraw our GPCR again 1 2 3 4 5 6 7 our seven alpha helixes now it's a little tougher to draw a conformational change but the protein is actually going to look completely different so here because of this binding we're going to have a conformational change the protein conformation of the GPCR will alter ok so let's just write out our first two steps real quick so step one we have the ligand binds to our GPCR step two we said that we undergo a conformational change so our gpcr undergoes conformational change what happens next is because of this conformational change our alpha subunit which I'm going to draw in here is actually going to exchange this gdp for GTP so just keep track step three our alpha subunit exchanges GDP for GTP so the molecule swapped out instead of GDP we have gtp now because we have gtp bound to this alpha subunit it'll now cause our alpha subunit to dissociate and move away from our beta and gamma subunit now once this happens these two different sections our alpha subunit and our beta gamma dimer these two together are actually going to find a protein in the membrane it's going to alter and regulate the function of that protein so we could have another protein for example here that the alpha subunit will find and regulate the function so let's go ahead and write this up step for our alpha subunit dissociates and regulates target proteins now during the step there are a few things I like to note the first is that both the alpha subunit and the beta gamma dimer can interact with other proteins to relay messages we're going to focus in on the alpha subunit because it tends to be more common and more however the beta gamma subunits can still regulate functions of other proteins the target proteins can be enzymes that produce second messengers which we'll talk a little more about in a second or ion channels that also let ions be second messengers now as we mentioned G proteins are incredibly diverse some G proteins can stimulate activity while others can also inhibit now step 5 once this alpha subunit activates a target protein this target protein can then relay a signal as long as this ligand is bound to the GPCR this process where´s alpha subunit dissociates looks for protein and regulates that target protein causing a whole chain of events can happen repeatedly as long as this ligand is bound now how can we actually make this thing go back to normal well step 6 is that our GTP is hydrolyzed to GDP so our gtp loses a phosphate and hydrolysis and becomes GDP once this happens ever thing goes back to normal and the ligand will leave and everything will go back to looking the way it was and ready to combine with another ligand in the future this often happens on its own eventually the gtp will be hydrolyzed and become GDP though our body actually has a few ways to regulate this one common way out of a few is the RGS protein which is regulation of g-protein signaling and this can accelerate this step now that we actually know the steps to this let's talk about an example a very common example of GPC our function in our cell actually involves epinephrine or adrenaline this is our fight-or-flight response so let's pretend that this green ligand this green signaling molecule is epinephrine and let's pretend that our GPCR is our adrenergic receptor once this epinephrine binds to our adrenergic receptor our GPCR in our body that binds epinephrine this adrenergic receptor will undergo a conformational change it will swap out this gdp on this alpha subunit for GTP and this alpha subunit will now seek out this other protein and regulate its function and it just so happens that the protein that it seeks out is going to be called adenylate cyclase now we have our adenylate cyclase being activated stimulated by our alpha subunit and what the identity cyclase will do is it will take ATP adenosine triphosphate and it will produce CA MP cyclic adenosine monophosphate so it'll take away 2 phosphates from our triphosphate and it'll make it mono phosphate once this happens our cyclic EMP here is what we call a second messenger so our signal our epinephrine goes through this entire process and the signal is transformed into another signal this cyclic ANP which is now inside our cells and this cyclic EMP will now tell our cell to do other things for example is that it'll increase our heart rate it'll also dilate our skeletal muscle blood vessels remember fight-or-flight we need to start running or fighting and so our muscles are going to have their blood vessels dilate and finally all of this process is going to require a lot of energy so we're going to actually break down glycogen to glucose now remember this is the biggest group of some lemon receptors it's a pretty complicated process just go over it again for example our epinephrine binds to our gpcr this gpcr then changes its shape and undergoes a conformational change it switches out the gdp to GTP on the alpha subunit which causes our alpha subunit to dissociate which will then regulate another protein and this protein will turn ATP into cyclic EMP which is our second messenger and this second messenger will now tell our body to do other things for example increase heart rate dilate blood vessels break down glycogen into glucose now other gpcrs in our body the other night 1000 are going to do other things but undergo a similar process so in summary GPCRs are a large diverse family of cell surface receptors that respond to many different external signals binding of our signaling molecule or are likened to our GPC our results in g-protein activation which then triggers the production of other second messengers using the sequence of events GPCRs can regulate an incredible range of bodily functions from sensation to growth to even hormone response
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