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In signalling pathways, G-proteins act as transducers and convert signals from one form to another form, by binding to other proteins in the plasma membrane of a cell, initiating a series of cascading reactions which lead to the expression of a cellular or physiological response. G-proteins can be either trimeric or monomeric. Monomeric G-proteins transduce signals from enzyme-linked receptors whereas trimeric G-proteins transduce signals from G-protein linked receptors. 



The central aspect to the signaling mechanism in which G-protein coupled receptors is that ligand do not diffuse through the plasma membrane upon binding. Rather, the signal is transmitted into the cell through a series of conformational changes that occur in the receptor protein itself, where agonist-binding events occur. Agonists are molecules which initiate a cellular or physiological response when bound to a receptor. Each receptor has a high affinity for a small range of similar agonists which are able to bind to an extracellular domain located outside the plasma membrane. The receptor protein is dynamic in that it is able to take on several conformations, 2 of the most prominent being active and inactive conformations[1]. Binding of the agonist favours the active conformation and this increases the affinity for G-protein binding on the inside of the cell. Once the ligand binds to the receptor, allosteric changes in the array of side-chain interactions around the extracellular agonist-binding site causes its tertiary structure to alter and creates large structural changes on the intracellular side, revealing a binding site for the G-protein to bind. This is the basis of transmission of an extracellular signal and its propagation into an intracellular one.


Binding of the ligand to the associated G-protein coupled receptor, GCPR, triggers an allosteric change in the G-protein causing it to release GDP, guanine di-phosphate, and binds GTP, guanine tri-phosphate. This allows the receptor to act as a guanine nucleotide exchange factor (GEF), responsible for the exchange of GDP for GTP in heterotrimeric proteins More specifically the release and binding of GDP and GTP respectively occurs in one of the G-protein’s three subunits, the a subunit, known as Ga. GTP binding causes Ga to dissociate from the other 2 subunits, Gβ and Gγ, which remain linked as a dimer after dissociation[2]. Each complex goes on to activate other effector molecules within the signaling pathway. This also allows the receptor to be able to activate the subsequent G-protein.


In order for the transduced signal to be terminated, the Ga subunit hydrolyzes the GTP molecule to GDP. This reaction is regulated by the enzymatic activity of GTPase-activating proteins (GAP’s) which are specific to the Ga subunit. These catalyze the hydrolysis of GTP to GDP causing the Ga subunit to become inactive. Once this occurs, all three subunits, G and GβGγ, re-associate into one complex and are arranged for the next transmitted signal in .

Example of G-protein functioning within the body

Ion channels can be activated by the binding of G-proteins. An example of this can be seen with adrenergic receptors, specialized muscarinic receptors, found in cardiac msucle. Binding of ligands to this receptor causes a decrease in heart rate, as the transduction of the signal increases the permeability of a neurone to K+ ions, which decreases the rate of neurone firing [3]. The release of K+ ions out of the cell increases the polarity within the cell reducing the chances of an action potential being generated. 


  1. Kobilka et. al (2004) Agonist Binding: A Multistep Process, Perspective (Online), Vol. 65 (5) p. 1060-1062 Available from: http://med.stanford.edu/kobilkalab/pdf/KobilkaMPNV.pdf
  2. Angers S, Salahpour A, Bouvier M. (2002) Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function, Annu Rev Pharmacol Toxicol, Vol.42 (409-35)
  3. Purves D, Augustine GJ, Fitzpatrick D, et al (2001) Neuroscience (2nd ed.) Sunderland MA: Sinauer Associates

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