View source for Trimeric G-protein

Trimeric G Proteins are usually found coupled to a receptor protein and attached to the [[Cytoplasmic face|cytoplasmic face]] of the [[Cell membrane|plasma membrane]]. It's function is to couple the receptor molecule to either an [[Ion channel|ion channel]] or [[Enzymes|enzyme]] (target signal Protein) where it acts as a relay Protein&nbsp;<ref>Cell Signalling: 3.2 Trimeric G Proteins. Available at http://www.open.edu/openlearn/science-maths-technology/cell-signalling/content-section-3.2fckLR 27/11/15</ref>.&nbsp;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|GDP]], when the coupled receptor is activated this alpha sub-unit releases this GDP molecule. A [[GTP|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|enzymes]], this therefore carries the signal forward and the result is a cell response <ref>Molecular Biology of The Cell 5th Edition Alberts et Al Pg 905</ref>.<br> 

An example of this is the activation of [[Adenylyl cyclase|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|epinephrine]] to the [[GPCR|G-protein coupled receptor]]. Interaction with the alpha subunit with adenylyl cyclase activates this enzyme which will then convert [[ATP|ATP]] within the cell to [[Cyclic AMP|cyclic AMP]]. This cyclic AMP is then responsible for activating [[Protein kinase A|protein kinase A]] which is involved in the [[Phosphorylation|phosphorylation]] of specific [[Protein kinase A|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 [[Cholera toxin|A subunit]] of the [[Cholera toxin|cholera toxin]] catalyzes the [[ADP-ribosylation|ADP-ribosylation]] of the trimeric G-protein [[Gs|Gs]]. This means the alpha subunit can no longer hydrolise [[ATP|ATP]] to [[ADP-ribosylation|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 <ref>page 1270, Molecular Biology of the Cell 6th Ed., 2015</ref>. 

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