View source for 7tqv


==SARS-CoV-2 endoribonuclease Nsp15 bound to dsRNA==
<StructureSection load='7tqv' size='340' side='right'caption='[[7tqv]], [[Resolution|resolution]] 3.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tqv]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.43&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqv OCA], [https://pdbe.org/7tqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqv RCSB], [https://www.ebi.ac.uk/pdbsum/7tqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqv ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is a uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.

Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease.,Frazier MN, Wilson IM, Krahn JM, Butay KJ, Dillard LB, Borgnia MJ, Stanley RE Nucleic Acids Res. 2022 Aug 12;50(14):8290-8301. doi: 10.1093/nar/gkac589. PMID:35801916<ref>PMID:35801916</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7tqv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Uridylate-specific endoribonuclease|Uridylate-specific endoribonuclease]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Synthetic construct]]
[[Category: Borgnia MJ]]
[[Category: Butay KJ]]
[[Category: Dillard LB]]
[[Category: Frazier MN]]
[[Category: Krahn JM]]
[[Category: Stanley RE]]