/lab/aaron-whiteley/ en /lab/aaron-whiteley/2023/07/26/bacterial-cgas-enzymes-produce-23-cgamp-activate-ion-channel-restricts-phage-replication <span>Bacterial cGAS-like enzymes produce 2鈥�,3鈥�-cGAMP to activate an ion channel that restricts phage replication</span> <span><span>Anonymous (not verified)</span></span> <span><time datetime="2023-07-26T10:44:22-06:00" title="Wednesday, July 26, 2023 - 10:44">Wed, 07/26/2023 - 10:44</time> </span> <div> <div class="imageMediaStyle focal_image_wide"> <img loading="lazy" src="/lab/aaron-whiteley/sites/default/files/styles/focal_image_wide/public/article-thumbnail/bacteria_synthesize_23-cgamp.png?h=817377e6&amp;itok=q9HcIB94" width="1200" height="800" alt="Bacteria Synthesize 2',3'-cGAMP"> </div> </div> <div role="contentinfo" class="container ucb-article-categories" itemprop="about"> <span class="visually-hidden">Categories:</span> <div class="ucb-article-category-icon" aria-hidden="true"> <i class="fa-solid fa-folder-open"></i> </div> <a href="/lab/aaron-whiteley/taxonomy/term/349"> Research Articles </a> </div> <div role="contentinfo" class="container ucb-article-tags" itemprop="keywords"> <span class="visually-hidden">Tags:</span> <div class="ucb-article-tag-icon" aria-hidden="true"> <i class="fa-solid fa-tags"></i> </div> <a href="/lab/aaron-whiteley/taxonomy/term/326" hreflang="en">2鈥�3鈥�-cGAMP</a> <a href="/lab/aaron-whiteley/taxonomy/term/285" hreflang="en">CBASS</a> <a href="/lab/aaron-whiteley/taxonomy/term/320" hreflang="en">Cap14</a> <a href="/lab/aaron-whiteley/taxonomy/term/217" hreflang="en">SAVED</a> <a href="/lab/aaron-whiteley/taxonomy/term/323" hreflang="en">Saf-2TM</a> <a href="/lab/aaron-whiteley/taxonomy/term/318" hreflang="en">antiphage signaling</a> <a href="/lab/aaron-whiteley/taxonomy/term/322" hreflang="en">biosensor</a> <a href="/lab/aaron-whiteley/taxonomy/term/163" hreflang="en">cGAS</a> <a href="/lab/aaron-whiteley/taxonomy/term/321" hreflang="en">ion channel</a> <a href="/lab/aaron-whiteley/taxonomy/term/324" hreflang="en">ligand-gated</a> <a href="/lab/aaron-whiteley/taxonomy/term/319" hreflang="en">phage</a> </div> <a href="/lab/aaron-whiteley/uday-tak">Uday Tak</a> <span>,&nbsp;</span> <a href="/lab/aaron-whiteley/peace-holguin-walth">Peace Holguin-Walth</a> <span>,&nbsp;</span> <a href="/lab/aaron-whiteley/aaron-whiteley">Aaron Whiteley</a> <div class="ucb-article-content ucb-striped-content"> <div class="container"> <div class="paragraph paragraph--type--article-content paragraph--view-mode--default 3"> <div class="ucb-article-row-subrow row"> <div class="ucb-article-text col-lg d-flex align-items-center" itemprop="articleBody"> <div><p><em>BioRxiv</em> (2023) <span>PubMed PMID: 37546940; PubMed Central PMCID: PMC10402079.</span></p><h2>Abstract</h2><p>The mammalian innate immune system uses cyclic GMP鈥揂MP synthase (cGAS) to synthesize the cyclic dinucleotide 2鈥�,3鈥�-cGAMP during antiviral and antitumor immune responses. 2鈥�,3鈥�-cGAMP is a nucleotide second messenger that initiates inflammatory signaling by binding to and activating the stimulator of interferon genes (STING) receptor. Bacteria also encode cGAS/DncV-like nucleotidyltransferases (CD-NTases) that produce nucleotide second messengers to initiate antiviral (antiphage) signaling. Bacterial CD-NTases produce a wide range of cyclic oligonucleotides but have not been documented to produce 2鈥�,3鈥�-cGAMP. Here we discovered bacterial CD-NTases that produce 2鈥�,3鈥�-cGAMP to restrict phage replication. Bacterial 2鈥�,3鈥�-cGAMP binds to CD-NTase associated protein 14 (Cap14), a transmembrane protein of unknown function. Using electrophysiology, we show that Cap14 is a chloride-selective ion channel that is activated by 2鈥�,3鈥�-cGAMP binding. Cap14 adopts a modular architecture, with an N-terminal transmembrane domain and a C-terminal nucleotide-binding SAVED domain. Domain-swapping experiments demonstrated the Cap14 transmembrane region could be substituted with a nuclease, thereby generating a biosensor that is selective for 2鈥�,3鈥�-cGAMP. This study reveals that 2鈥�,3鈥�-cGAMP signaling extends beyond metazoa to bacteria. Further, our findings suggest that transmembrane proteins of unknown function in bacterial immune pathways may broadly function as nucleotide-gated ion channels.</p><h2>News and Commentaries</h2><ul><li><a href="https://twitter.com/snowkaryote/status/1683882461128953856?s=20" rel="nofollow">Read Uday's Tweetorial </a>[Twitter]</li></ul><h2>Links&nbsp;</h2><ul><li>DOI:&nbsp;<a href="https://doi.org/10.1101/2023.07.24.550367" rel="nofollow">https://doi.org/10.1101/2023.07.24.550367</a></li><li>Journal Link:&nbsp;</li><li><em>BioRxiv</em> Preprint, July 24 2023, <a href="https://doi.org/10.1101/2023.07.24.550367" rel="nofollow">https://doi.org/10.1101/2023.07.24.550367</a></li></ul><h2>Citation</h2><p><span>Tak U, Walth P, Whiteley AT. </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/37546940/" rel="nofollow">Bacterial cGAS-like enzymes produce 2',3'-cGAMP to activate an ion channel that restricts phage replication.</a><span>bioRxiv. 2023 Jul 24;. doi: 10.1101/2023.07.24.550367. PubMed PMID: 37546940; PubMed Central PMCID: PMC10402079.</span></p></div> </div> <div class="ucb-article-content-media ucb-article-content-media-right col-lg"> <div> <div class="paragraph paragraph--type--media paragraph--view-mode--default"> <div> <div class="imageMediaStyle large_image_style"> <img loading="lazy" src="/lab/aaron-whiteley/sites/default/files/styles/large_image_style/public/article-image/website_biorxivcap14_resize.jpg?itok=dBydSPPI" width="1500" height="1003" alt="Bacteria Synthesize 2',3'-cGAMP"> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>Tak U, Walth P, 鉃hiteley AT | BioRxiv 2023</div> <h2> <div class="paragraph paragraph--type--ucb-related-articles-block paragraph--view-mode--default"> <div>Off</div> </div> </h2> <div>Traditional</div> <div>0</div> <div>On</div> <div>White</div> Wed, 26 Jul 2023 16:44:22 +0000 Anonymous 175 at /lab/aaron-whiteley