G protein signalling pathway step by step please?

1. Signalling molecule outside the cell binds to the G-protein coupled receptor in the cell surface membrane, causing it to change shape (confirmational change)
2. This causes a bound molecule of GDP to be phosphorylated to GTP inside the cell
3. GTP binds to adenyl cyclase, a transmembrane protein, causing it to change shape
4. Adenyl cyclase converts ATP to the secondary messenger cAMP
5. cAMP diffuses through the cytosol and activated protein kinase enzymes (which act as "on switches" for proteins)
6. More and more kinases are activated, creating a cascade of enzyme activation
7. The target proteins are activated and do their job in the cell (eg glycogen synthase)
There's a good animation of this process here: https://highered.mheducation.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors_that_activate_g_proteins.html
Do check with your specific exam board how they want to phrase this/the key words etc!
Also this is to A level standard, it's obviously more complicated than this :smile:

Reply 2

TheKitty.x

OP

14

Original post by becausethenight

1. Signalling molecule outside the cell binds to the G-protein coupled receptor in the cell surface membrane, causing it to change shape (confirmational change)
2. This causes a bound molecule of GDP to be phosphorylated to GTP inside the cell
3. GTP binds to adenyl cyclase, a transmembrane protein, causing it to change shape
4. Adenyl cyclase converts ATP to the secondary messenger cAMP
5. cAMP diffuses through the cytosol and activated protein kinase enzymes (which act as "on switches" for proteins)
6. More and more kinases are activated, creating a cascade of enzyme activation
7. The target proteins are activated and do their job in the cell (eg glycogen synthase)
There's a good animation of this process here: https://highered.mheducation.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors_that_activate_g_proteins.html
Do check with your specific exam board how they want to phrase this/the key words etc!
Also this is to A level standard, it's obviously more complicated than this :smile:

Wow thank you so much, is this good for level 4? :smile:

Reply 3

HarisMalik98

12

By level 4 do you mean university standard? If so there's a few extra bits I'd add in.

There are two main classes of G-proteins: The heterotrimeric "large" class and the "small" class.

The heterotrimeric is the classic type that functions through a GPCR and is detailed above. One addition to add though could be the structure of the G-protein itself. The G-protein is made up from an alpha, beta and gamma subunits - and this complex is associated with the GPCR. It is the ALPHA subunit that has the bound GDP. When the conformational change in the GPCR occurs and the Guanine Nucleotide Exchange Factor (GEF) domain is activated - it exchanges GDP for GTP on the G-Protein alpha subunit. The activated alpha subunit then dissociates from the beta-gamma dimer and the GPCR and goes on to activate downstream targets that have already been mentioned. I.e. the functional unit of the G-Protein is the Alpha subunit.

Also, the alpha subunits have intrinsic GTPase activity, meaning the bound GTP is eventually hydrolysed back to GDP and inactivates the G-protein (method of control). RGS proteins also act as GTPase-Activating Proteins (GAP) and can accelerate this intrinsic GTPase activity. This prevents constant stimulation of the pathway.

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The other class is the small G-Proteins. These are also involved in signalling cascades. However, they are exact homologs of the G-Protein alpha subunits meaning they are monomeric. They still bind GDP and GTP as normal to mediate activation and inactivation. They are located in the cytosol, where they allow the propagation of a signalling cascade.

As opposed to being activated by the GEF domain in the GPCR, small G-Proteins are activated by other GEFs. Like the heterotrimeric alpha subunits, they also have intrinsic GTPase activity and associated GAP proteins to inactivate them.

An example is the Ras GTPases. Ras GTPases propagate cascades that activate pathways such as the MAP kinase pathway and the cell cycle regulatory pathway (PI3K/Akt/mTOR). I suggest looking up the Ras GTPases to appreciate the variety of pathways they are integral to.

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Also for university level I'd imagine they would want you to know a couple of examples of downstream molecules activated by G-Proteins and what cellular functions they carry out. There are two main secondary messenger pathways:

-Adenylate Cyclase/cAMP/PKA Pathway
E.g. Pathway for ADH, LH and Glucagon

-PLC/PiP2/IP3/DAG Pathway
E.g. Pathway for GnRH and TRH

There are many many different examples though - and often lots of crossover between the pathways in terms of what they activate. Google can be your friend there though! Hopefully the mechanisms are clear now though.

(edited 3 years ago)

G protein signalling pathway step by step please?

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