Trimeric G-protein

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Trimeric G Proteins are usually found coupled to a receptor protein and attached to the cytoplasmic face of the plasma membrane. It's function is to couple the receptor molecule to either an ion channel or enzyme (target signal Protein) where it acts as a relay Protein.[1]Trimeric G Proteins are composed of three sub-units, alpha beta and gamma. In its inactive state the alpha sub-unit is bound to GDP, when the coupled receptor is activated this alpha sub-unit releases this GDP molecule. A GTP molecule takes the place of the GDP on the alpha sub-unit and the protein under goes a large conformational change; the G protein is now in it's activated state. The sub-units dissociate into an alpha sub-unit and a beta-gamma complex which then go on to activate their target molecules which may be enzymes, this therefore carries the signal forward and the result is a cell response [2].

An example of this is the activation of adenylyl cyclase through the dissociation of the beta and alpha subunit that occurs as a result of the activation of a g-protein through the binding of epinephrine to the G-protein coupled receptor. Interaction with the alpha subunit with adenylyl cyclase activates this enzyme which will then convert ATP within the cell to cyclic AMP. This cyclic AMP is then responsible for activating protein kinase A which is involved in the phosphorylation of specific protein in the cell, thus triggering a cellular response. This response is dependant upon the protein phosphorylated and the identity of the cell itself.

The A subunit of the cholera toxin catalyzes the ADP-ribosylation of the trimeric G-protein Gs. This means the alpha subunit can no longer hydrolise ATP to ADP and Pi. Hense adenyle cyclase is constantly activated. cAMP levels rise beyond what is 'normal' in the cell resulting in a phospherylation cascade- eventually resulting in the release of ions and water into the intestinal lumen, leading to watery diarrhea that is aassociated with Cholera.


1- page 1270, Molecular Biology of the Cell 6th Ed., 2015

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