8d4b
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8d4b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Sulfuricurvum_sp._PC08-66 Sulfuricurvum sp. PC08-66] 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=8D4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D4B FirstGlance]. <br> | <table><tr><td colspan='2'>[[8d4b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Sulfuricurvum_sp._PC08-66 Sulfuricurvum sp. PC08-66] 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=8D4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D4B FirstGlance]. <br> | ||
| - | </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=8d4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d4b OCA], [https://pdbe.org/8d4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d4b RCSB], [https://www.ebi.ac.uk/pdbsum/8d4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d4b ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.92Å</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=8d4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d4b OCA], [https://pdbe.org/8d4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d4b RCSB], [https://www.ebi.ac.uk/pdbsum/8d4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d4b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/A0A0C2W1L1_9PROT A0A0C2W1L1_9PROT] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection(1). Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of 'aromatic clamp' residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates. | Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection(1). Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of 'aromatic clamp' residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates. | ||
| - | RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.,Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW Nature. 2023 Jan | + | RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.,Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW Nature. 2023 Jan;613(7944):582-587. doi: 10.1038/s41586-022-05560-w. Epub 2023 , Jan 4. PMID:36599980<ref>PMID:36599980</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Revision as of 05:19, 12 June 2024
Structure of Cas12a2 ternary complex
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