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4.13: G Proteins

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    Figure \(\PageIndex{1}\): G Proteins

    G proteins are so-called because they bind the guanine nucleotides GDP and GTP. They are heterotrimers (i.e., made of three different subunits) associated with the inner surface of the plasma membrane and transmembrane receptors of hormones, etc. These are called G protein-coupled receptors (GPCRs).

    The three subunits are:

    • Gα, which carries the binding site for the nucleotide. At least 20 different kinds of Gα molecules are found in mammalian cells.

    How G Proteins Work

    • In the inactive state, Gα has GDP in its binding site.
    • When a hormone or other ligand binds to the associated GPCR, an allosteric change takes place in the receptor (that is, its tertiary structure changes).
    • This triggers an allosteric change in Gα causing
    • GDP to leave and be replaced by GTP.
    • GTP activates Gα causing it to dissociate from GβGγ (which remain linked as a dimer).
    • Activated Gα in turn activates an effector molecule.

      In a common example (shown here), the effector molecule is adenylyl cyclase - an enzyme in the inner face of the plasma membrane which catalyzes the conversion of ATP into the "second messenger" cyclic AMP (cAMP).

    Activated Gα is a GTPase so it quickly converts its GTP to GDP. This conversion, coupled with the return of the Gβ and Gγ subunits, restores the G protein to its inactive state.

    Some Types of Gα Subunits


    This type stimulates (s = "stimulatory") adenylyl cyclase. It is the one depicted here. It is associated with the receptors for many hormones such as:

    • adrenaline
    • glucagon
    • luteinizing hormone (LH)
    • parathyroid hormone (PTH)
    • adrenocorticotropic hormone (ACTH)

    s is the target of the toxin liberated by Vibrio cholerae, the bacterium that causes cholera. Binding of cholera toxin to Gαs keeps it turned "on". The resulting continuous high levels of cAMP causes a massive loss of salts from the cells of the intestinal epithelium. Massive amounts of water follow by osmosis causing a diarrhea that can be fatal if the salts and water are not quickly replaced.


    This activates phospholipase C (PLC) which generates the second messengers:

    • inositol trisphosphate (IP3)
    • diacylglycerol (DAG)

    q is found in G proteins coupled to receptors for vasopressin, thyroid-stimulating hormone (TSH), and angiotensin.


    This inhibits (i = "inhibitory") adenylyl cyclase lowering the level of cAMP in the cell. Gai is activated by the receptor for somatostatin.


    The "t" is for transducin, the molecule responsible for generating a signal in the rods of the retina in response to light. Gαt triggers the breakdown of cyclic GMP (cGMP).

    This page titled 4.13: G Proteins is shared under a CC BY 3.0 license and was authored, remixed, and/or curated by John W. Kimball via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request.

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