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Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense
/lab/aaron-whiteley/2021/06/01/molecular-basis-cd-ntase-nucleotide-selection-cbass-anti-phage-defense
<span>Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense</span>
<span><span>Anonymous (not verified)</span></span>
<span><time datetime="2021-06-01T00:00:00-06:00" title="Tuesday, June 1, 2021 - 00:00">Tue, 06/01/2021 - 00:00</time>
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<a href="/lab/aaron-whiteley/taxonomy/term/285" hreflang="en">CBASS</a>
<a href="/lab/aaron-whiteley/taxonomy/term/286" hreflang="en">anti-phage</a>
<a href="/lab/aaron-whiteley/taxonomy/term/219" hreflang="en">nucleotide second messenger</a>
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<span>Govande AA</span>
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<span>Duncan-Lowey B</span>
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<span>Eaglesham JB</span>
<span>, </span>
<a href="/lab/aaron-whiteley/aaron-whiteley">Aaron Whiteley</a>
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<span>Kranzusch PJ</span>
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<div><p><em>Cell Reports</em> (2021) <span>PubMed PMID: </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/34077735/" rel="nofollow"><span>34077735</span></a></p><h2>Abstract</h2><p>cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are signaling proteins that initiate antiviral immunity in animal cells and cyclic-oligonucleotide-based anti-phage signaling system (CBASS) phage defense in bacteria. Upon phage recognition, bacterial CD-NTases catalyze synthesis of cyclic-oligonucleotide signals, which activate downstream effectors and execute cell death. How CD-NTases control nucleotide selection to specifically induce defense remains poorly defined. Here, we combine structural and nucleotide-analog interference-mapping approaches to identify molecular rules controlling CD-NTase specificity. Structures of the cyclic trinucleotide synthase Enterobacter cloacae CdnD reveal coordinating nucleotide interactions and a possible role for inverted nucleobase positioning during product synthesis. We demonstrate that correct nucleotide selection in the CD-NTase donor pocket results in the formation of a thermostable-protein-nucleotide complex, and we extend our analysis to establish specific patterns governing selectivity for each of the major bacterial CD-NTase clades A-H. Our results explain CD-NTase specificity and enable predictions of nucleotide second-messenger signals within diverse antiviral systems.</p><h2>Links </h2><ul><li>DOI: <a href="https://doi.org/10.1016/j.celrep.2021.109206" rel="nofollow">10.1016/j.celrep.2021.109206</a></li><li>Journal Link: <a href="https://www.sciencedirect.com/science/article/pii/S2211124721005556" rel="nofollow">https://www.sciencedirect.com/science/article/pii/S2211124721005556</a></li></ul><h2>Citation</h2><p><span>Govande AA, Duncan-Lowey B, Eaglesham JB, Whiteley AT, Kranzusch PJ. </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/34077735/" rel="nofollow">Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense. </a><span>Cell Rep. 2021 Jun 1;35(9):109206. doi: 10.1016/j.celrep.2021.109206. PubMed PMID: 34077735.</span></p></div>
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<div>Govande AA, Duncan-Lowey B, Eaglesham JB, 鉃hiteley AT, Kranzusch PJ. | Cell Reports 2021</div>
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Tue, 01 Jun 2021 06:00:00 +0000
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