G Protein linked 2nd Messengers, G protein coupled receptors, GPCRs

Understand the G-protein receptors like never before!!!
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I'm sure that you've talked about the G protein-linked receptors in school, however, you might not have called them G protein-linked receptors.
They go by other names like G protein-linked second messengers or G protein-coupled receptors, that's a pretty common one.
Even conversationally, a lot of people just say the G proteins.
I'm gonna break down those words a little bit later and tell you what each part of it means and why we use those names to refer to these proteins.
But first off, what does the G stand for? Why is it G protein? Well, the G stands for guanine.
These are guanine nucleotide-binding proteins, meaning that they bind guanine nucleotides.
Like for example guanosine triphosphate or its slightly shorter little brother, guanosine diphosphate.
These receptors are extremely important physiologically.
We use them all over our body and they do all kinds of different functions.
These receptors are only found in eukaryotes and are the target of about 40% of all the drugs we use in medicine today.
I just told you that they're very diverse in function however, there's two main signal transduction pathways that you got to know, you have to know them for your boards and that is the cyclic AMP-dependent pathway and the phosphatidylinositol signal pathway, okay? I'll talk about those more in a little bit.
First, let's jump into the structure and function of these things, it's pretty cool.
I told you that I was going to breakdown the names so that you can understand the concepts a little bit better.
First off, let's get started with what does the word "G proteins" mean? Well, the G proteins are a component of this receptor system.
The G proteins are heterotrimeric GTP-binding proteins made of three subunits, hence, heterotrimeric.
First there's the alpha subunit, then the beta subunit and then the gamma subunit.
And you should also notice from my illustration here that the beta and gamma subunits are more tightly linked together than the two are to the alpha subunit.
Actually the beta and the gamma stay connected where the alpha subunit separates itself in normal function.
These G proteins live on the intracellular side of the cell membrane and are attached to or connected to the cell membrane itself by lipid anchors.
The next thing for us to talk about is to define what are the G protein-coupled receptors? Well, these are receptors that live in the membrane and in fact, they pass through the membrane seven times which is an important number, you might be tested on it.
All right, so these G protein-coupled receptors interact with the G proteins and cause oftentimes a confirmational change so that the alpha subunit of the G protein can accept different nucleotides.
What about the term G protein-linked second messengers? Well, that's another component of this system which are cellular target-proteins or enzymes that perform some kind of function when they interact with the G proteins that we've already talked about.
Now they are very diverse but as I said in the beginning, there's two main pathways or two main targets that cause a pathway that you have to understand.
And those two are the cyclic AMP-dependent pathway and the phosphatidylinositol signal pathway, which I abbreviate here as IP3/DAG pathway.
Right now you're probably thinking, Dr. Joel, I have no idea what you're talking about.
Don't worry, I will show you the whole thing working and we'll talk about the parts as we go, and I'm pretty sure that it will make sense after we go through it.
First, we have to set the stage a little bit.
The G proteins or more specifically, the alpha subunit of the G proteins is bound in its resting state to guanosine diphosphate or GDP.
In this state, the receptor is just sitting and waiting.
On the extracellular side of the cell membrane, a ligand comes and it binds with the G protein-coupled receptor causing a confirmational change.
The confirmational change allows the alpha subunit to bind with guanosine triphosphate and release the guanosine diphosphate.
Now, the G proteins are active and as active G proteins, they do a couple of things.
First off, the alpha subunit separates itself from the beta gamma complex.
This kind of frees it up a little bit so it's free to move around.
It's still attached to the membrane by a lipid anchor but the lipid anchor can kind of swim through the membranes.
It's able to move to the target.
It moves the target and it causes the target protein or enzyme to change in some way.
Either the G protein interaction causes the target to speed up what it's doing or slow down what it's doing or stop what it's doing.
It does something to the target protein.

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Clear and concise video on GPCR! Your mnemonics are very helpful for long term use past the Boreds - ie useful on Rounds too! Thanks so much. I hope you are at a Teaching Hospital and Medical students are able to benefit from your knowledge and expertise at explaining that knowledge to others.
God Bless you! I’m a retired physician and we didn’t know much of what we now know in terms of molecular biology and it’s applications to clinical medicine. But Med school taught me how to learn and so I continue to learn! Thanks for being a part of another physician’s education. You are fulfilling the Oath!
Thank you. God Bless!

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I am honestly grateful for this video. I've watched so many others on this same topic, but this one was by far the BEST. I finally understand this topic!!

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Thank you! I now understand G-receptors like never before :)

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THANK YOU!! That helped a lot! I understand the thing now. Thank you very much and good luck with your residency...

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Thanks sir it help me alot in building my understanding on signal transduction
The way u explain n mnemonics was outstanding.

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Detailed, clear, and definitely easy to understand!! Thank you!!! Can you please make a video on action potential?

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I think it's helpful to note that the separation of the beta/gamma complex increases the alpha's affinity for GTP... perhaps helpful to me at least :[

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YOU ARE MY HERO! I am finishing my 3rd week of med school and we got taught 5 of these types of pathways in less than 2 hours. That did NOT stick in my brain.This video was great, now I am going to see if you have one on MAPK, PI3K/Akt, and Wnt/B-catenin!

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GPCRs are found in yeast, choanoflagellates, and animals. Ligands that bind and activate GPCRs include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and range from small molecules, peptides to large proteins.

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Once we understand all the receptors , the later will be easy to remember all the medication uses and side effects

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What would be an example of cellular responses in G- protein linked receptors? Thank you for an amazing video!

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