8d4b: Difference between revisions
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==Structure of Cas12a2 ternary complex== | |||
<StructureSection load='8d4b' size='340' side='right'caption='[[8d4b]], [[Resolution|resolution]] 2.92Å' scene=''> | |||
== 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> | |||
</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> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0C2W1L1_9PROT A0A0C2W1L1_9PROT] | |||
<div style="background-color:#fffaf0;"> | |||
== 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. | |||
RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.,Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW Nature. 2023 Jan 4. doi: 10.1038/s41586-022-05560-w. PMID:36599980<ref>PMID:36599980</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Bravo | <div class="pdbe-citations 8d4b" style="background-color:#fffaf0;"></div> | ||
[[Category: Taylor | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Sulfuricurvum sp. PC08-66]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Bravo JPK]] | |||
[[Category: Taylor DW]] | |||
Revision as of 07:30, 18 January 2023
Structure of Cas12a2 ternary complex
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