/lab/aaron-whiteley/ en /lab/aaron-whiteley/2019/03/01/bacterial-cgas-enzymes-synthesize-diverse-nucleotide-signals <span>Bacterial cGAS-like enzymes synthesize diverse nucleotide signals</span> <span><span>Anonymous (not verified)</span></span> <span><time datetime="2019-03-01T00:00:00-07:00" title="Friday, March 1, 2019 - 00:00">Fri, 03/01/2019 - 00:00</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/cd-ntase_tree.png?h=4d0bd0b4&amp;itok=RbqTCtVI" width="1200" height="600" alt="CD-NTase Tree"> </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/153"> Spotlight Publications </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/143" hreflang="en">CD-NTase</a> <a href="/lab/aaron-whiteley/taxonomy/term/161" hreflang="en">RECON</a> <a href="/lab/aaron-whiteley/taxonomy/term/159" hreflang="en">STING</a> <a href="/lab/aaron-whiteley/taxonomy/term/163" hreflang="en">cGAS</a> <a href="/lab/aaron-whiteley/taxonomy/term/155" hreflang="en">cyclic oligonucleotides</a> <a href="/lab/aaron-whiteley/taxonomy/term/157" hreflang="en">innate immunity</a> <a href="/lab/aaron-whiteley/taxonomy/term/151" hreflang="en">second messenger signaling</a> </div> <span>➤Whiteley AT</span> <span>,&nbsp;</span> <span>&nbsp;Eaglesham JB</span> <span>,&nbsp;</span> <span>&nbsp;de Oliveira Mann CC</span> <span>,&nbsp;</span> <span>&nbsp;Morehouse BR</span> <span>,&nbsp;</span> <span>&nbsp;Lowey B</span> <span>,&nbsp;</span> <span>&nbsp;Nieminen EA</span> <span>,&nbsp;</span> <span>&nbsp;Danilchanka O</span> <span>,&nbsp;</span> <span>&nbsp;King DS</span> <span>,&nbsp;</span> <span>&nbsp;Lee ASY</span> <span>,&nbsp;</span> <span>&nbsp;Mekalanos JJ*</span> <span>,&nbsp;</span> <span>&nbsp;Kranzusch PJ*</span> <div class="ucb-article-content ucb-striped-content"> <div class="container"> <div class="paragraph paragraph--type--article-content paragraph--view-mode--default"> <div class="ucb-article-content-media ucb-article-content-media-above"> <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/cd-ntases_and_the_immune_system.png?itok=_6XirBnc" width="1500" height="689" alt="CD-NTases and the immune system"> </div> </div> </div> </div> </div> <div class="ucb-article-text d-flex align-items-center" itemprop="articleBody"> <div><p>*co-corresponding authors</p> <p><em>Nature</em>.&nbsp;2019 Mar;567(7747):194-199. doi: 10.1038/s41586-019-0953-5. Epub 2019 Feb 20.</p> <h3>Abstract</h3> <p>Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.</p> <h3>News and Commentaries</h3> <ul> <li><a href="https://doi.org/10.1016/j.chom.2019.03.016" target="_blank" rel="nofollow">Pyrimidines and Cyclic Trinucleotides Join the Second Messenger Symphony.</a> [<i>Cell host &amp; microbe</i>&nbsp;2019]</li> <li><a href="https://doi.org/10.1126/scisignal.aax3389" target="_blank" rel="nofollow">Diverse bacterial nucleotide signals.</a> [<em>Science Signaling</em>&nbsp;2019]</li> <li>Highlighted and discussed in&nbsp;<i>This Week In Microbiology</i>&nbsp;Podcast&nbsp;<a href="https://www.asm.org/Podcasts/TWiM/Episodes/Bacteria-send-nucleotide-signals-TWiM-206" rel="nofollow">Episode #206</a></li> </ul> <h3>Links</h3> <ul> <li>PMID:<a href="https://www.ncbi.nlm.nih.gov/pubmed/30787435" target="_blank" rel="nofollow">30787435</a></li> <li>PMCID:<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544370/" rel="nofollow">PMC6544370</a></li> <li>DOI:<a href="https://doi.org/10.1038/s41586-019-0953-5" target="_blank" rel="nofollow">10.1038/s41586-019-0953-5</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544370/" rel="nofollow">Free PMC Article</a></li> </ul></div> </div> </div> </div> </div> <div>➤Whiteley AT, Eaglesham JB, de Oliveira Mann CC, Morehouse BR, Lowey B, Nieminen EA, Danilchanka O, King DS, Lee ASY, Mekalanos JJ*, Kranzusch PJ* | Nature. 2019</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> Fri, 01 Mar 2019 07:00:00 +0000 Anonymous 9 at /lab/aaron-whiteley