4.13:_G_Proteins

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<figure><img class="internal" alt="Diagram showing a cell signaling pathway with a receptor, hormone, and G protein that activates adenylate cyclase. ATP converts to cAMP. 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data-semantic-role="integer" data-semantic-font="normal" data-semantic-annotation="clearspeak:simple;nemeth:number;depth:2" data-semantic-="" data-semantic-parent="5" data-semantic-attributes="latex:13" data-semantic-level-number="1" data-speech-node="true">13</mn><mrow data-mjx-texclass="ORD" data-latex="{.}"><mo data-latex="." data-semantic-type="punctuation" data-semantic-role="fullstop" data-semantic-annotation="nemeth:number;depth:2" data-semantic-="" data-semantic-parent="5" data-semantic-attributes="latex:{.};texclass:ORD" data-semantic-operator="punctuated" data-semantic-level-number="1" data-speech-node="true">.</mo></mrow><mn data-latex="1" data-semantic-type="number" data-semantic-role="integer" data-semantic-font="normal" data-semantic-annotation="clearspeak:simple;nemeth:number;depth:2" data-semantic-="" data-semantic-parent="5" data-semantic-attributes="latex:1" data-semantic-level-number="1" data-speech-node="true">1</mn></mrow></math></mjx-assistive-mml></mjx-container>: G Proteins</figcaption></figure>

<p class="lt-bio-4652" style="background-color: unset;">G proteins are so-called because they bind the <strong>g</strong>uanine nucleotides <strong>G</strong>DP and <strong>G</strong>TP. They are heterotrimers (i.e., made of three different subunits) associated with the inner surface of the plasma membrane and transmembrane <strong>receptors</strong> of hormones, etc. These are called G protein-coupled receptors (<strong>GPCR</strong>s).</p>

<p class="lt-bio-4652" style="background-color: unset;">The three subunits are:</p>

<ul>
    <li class="lt-bio-4652" style="background-color: unset;">G&alpha;, which carries the binding site for the nucleotide. At least 20 different kinds of G&alpha; molecules are found in mammalian cells.</li>
    <li class="lt-bio-4652" style="background-color: unset;">G&beta;</li>
    <li class="lt-bio-4652" style="background-color: unset;">G&gamma;</li>
</ul>

<span id="How_G_Proteins_Work"></span><span id="How_G_Proteins_Work"></span><h2 style="background-color: unset;" class="lt-bio-4652">How G Proteins Work</h2>

<ul>
    <li class="lt-bio-4652" style="background-color: unset;">In the inactive state, G&alpha; has <strong>GDP</strong> in its binding site.</li>
    <li class="lt-bio-4652" style="background-color: unset;">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).</li>
    <li class="lt-bio-4652" style="background-color: unset;">This triggers an allosteric change in G&alpha; causing</li>
    <li class="lt-bio-4652" style="background-color: unset;">GDP to leave and be replaced by <strong>GTP</strong>.</li>
    <li class="lt-bio-4652" style="background-color: unset;">GTP activates G&alpha; causing it to dissociate from G&beta;G&gamma; (which remain linked as a dimer).</li>
    <li class="lt-bio-4652" style="background-color: unset;">Activated G&alpha; in turn activates an effector molecule.
    <p class="lt-bio-4652" style="background-color: unset;">In a common example (shown here), the effector molecule is <strong>adenylyl cyclase</strong> - an enzyme in the inner face of the plasma membrane which catalyzes the conversion of ATP into the &quot;second messenger&quot; cyclic AMP (<strong>cAMP</strong>).</p>
    </li>
</ul>

<p class="lt-bio-4652" style="background-color: unset;">Activated G&alpha; is a GTPase so it quickly converts its GTP to GDP. This conversion, coupled with the return of the G&beta; and G&gamma; subunits, restores the G protein to its inactive state.</p>

<span id="Some_Types_of_G.CE.B1_Subunits"></span><span id="Some_Types_of_G.CE.B1_Subunits"></span><h2 style="background-color: unset;" class="lt-bio-4652">Some Types of G&alpha; Subunits</h2>

<span id="G.CE.B1s"></span><span id="G.CE.B1s"></span><h3 style="background-color: unset;" class="lt-bio-4652">G&alpha;<sub><font size="3">s</font></sub></h3>

<p class="lt-bio-4652" style="background-color: unset;">This type <strong>stimulates</strong> (<strong>s</strong> = &quot;stimulatory&quot;) adenylyl cyclase. It is the one depicted here. It is associated with the receptors for many hormones such as:</p>

<ul>
    <li class="lt-bio-4652" style="background-color: unset;">adrenaline</li>
    <li class="lt-bio-4652" style="background-color: unset;">glucagon</li>
    <li class="lt-bio-4652" style="background-color: unset;">luteinizing hormone (<strong>LH</strong>)</li>
    <li class="lt-bio-4652" style="background-color: unset;">parathyroid hormone (<strong>PTH</strong>)</li>
    <li class="lt-bio-4652" style="background-color: unset;">adrenocorticotropic hormone (<strong>ACTH</strong>)</li>
</ul>

<p class="lt-bio-4652" style="background-color: unset;">G&alpha;<sub><strong><font size="2">s</font></strong></sub> is the target of the toxin liberated by Vibrio cholerae, the bacterium that causes <strong>cholera</strong>. Binding of cholera toxin to G&alpha;<sub><strong><font size="2">s</font></strong></sub> keeps it turned &quot;on&quot;. 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.</p>

<span id="G.CE.B1q"></span><span id="G.CE.B1q"></span><h3 style="background-color: unset;" class="lt-bio-4652">G&alpha;<sub><font size="3">q</font></sub></h3>

<p class="lt-bio-4652" style="background-color: unset;">This activates <strong>phospholipase C</strong> (PLC) which generates the second messengers:</p>

<ul>
    <li class="lt-bio-4652" style="background-color: unset;">inositol trisphosphate (<strong>IP<sub><font size="2">3</font></sub></strong>)</li>
    <li class="lt-bio-4652" style="background-color: unset;">diacylglycerol (<strong>DAG</strong>)</li>
</ul>

<p class="lt-bio-4652" style="background-color: unset;">G&alpha;<sub><font size="2">q</font></sub> is found in G proteins coupled to receptors for vasopressin, thyroid-stimulating hormone (<strong>TSH</strong>), and angiotensin.</p>

<span id="G.CE.B1i"></span><span id="G.CE.B1i"></span><h3 style="background-color: unset;" class="lt-bio-4652">G&alpha;<sub><font size="3">i</font></sub></h3>

<p class="lt-bio-4652" style="background-color: unset;">This <strong>inhibits</strong> (<strong>i</strong> = &quot;inhibitory&quot;) adenylyl cyclase lowering the level of cAMP in the cell. G<span style="font-family:symbol;">a</span><sub><font size="2">i</font></sub> is activated by the receptor for somatostatin.</p>

<span id="G.CE.B1t"></span><span id="G.CE.B1t"></span><h3 style="background-color: unset;" class="lt-bio-4652">G&alpha;<sub><font size="3">t</font></sub></h3>

<p class="lt-bio-4652" style="background-color: unset;">The &quot;t&quot; is for <strong>transducin</strong>, the molecule responsible for generating a signal in the rods of the retina in response to light. G&alpha;<sub><font size="2">t</font></sub> triggers the breakdown of <strong>cyclic GMP</strong> (cGMP).</p>

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<hr class="autoattribution-divider" /><div class="autoattribution"><p>This page titled <a target="_blank" class="internal mt-self-link" href="/Sandboxes/johnnyphung/biology/04:_Cell_Metabolism/4.13:_G_Proteins">4.13: G Proteins</a> is shared under a <a rel="nofollow" href="https://creativecommons.org/licenses/by/3.0" target="_blank">CC BY  3.0</a>  license and was authored, remixed, and/or curated by <a rel="nofollow" target="_blank" href="http://www.biology-pages.info/">John W. Kimball</a> via <a rel="nofollow" href="https://www.biology-pages.info/" target="_blank">source content</a> that was edited to the style and standards of the LibreTexts platform.</p></div>

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