7tr9: Difference between revisions
New page: '''Unreleased structure''' The entry 7tr9 is ON HOLD Authors: Hu, C., Ni, D., Nam, K.H., Majumdar, S., McLean, J., Stahlberg, H., Terns, M., Ke, A. Description: Cascade complex from ty... |
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The | ==Cascade complex from type I-A CRISPR-Cas system== | ||
<StructureSection load='7tr9' size='340' side='right'caption='[[7tr9]], [[Resolution|resolution]] 3.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7tr9]] is a 19 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Escherichia_coli_#1/H766 Escherichia coli #1/H766] and [https://en.wikipedia.org/wiki/Pyrococcus_furiosus_DSM_3638 Pyrococcus furiosus DSM 3638]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TR9 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]] 3.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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=7tr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tr9 OCA], [https://pdbe.org/7tr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tr9 RCSB], [https://www.ebi.ac.uk/pdbsum/7tr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tr9 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degradation. Contrary to this model, here, we show that type I-A Cascade and Cas3 function as an integral effector complex. We provide four cryoelectron microscopy (cryo-EM) snapshots of the Pyrococcus furiosus (Pfu) type I-A effector complex in different stages of DNA recognition and degradation. The HD nuclease of Cas3 is autoinhibited inside the effector complex. It is only allosterically activated upon full R-loop formation, when the entire targeted region has been validated by the RNA guide. The mechanistic insights inspired us to convert Pfu Cascade-Cas3 into a high-sensitivity, low-background, and temperature-activated nucleic acid detection tool. Moreover, Pfu CRISPR-Cas3 shows robust bi-directional deletion-editing activity in human cells, which could find usage in allele-specific inactivation of disease-causing mutations. | |||
Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools.,Hu C, Ni D, Nam KH, Majumdar S, McLean J, Stahlberg H, Terns MP, Ke A Mol Cell. 2022 Aug 4;82(15):2754-2768.e5. doi: 10.1016/j.molcel.2022.06.007. Epub , 2022 Jul 13. PMID:35835111<ref>PMID:35835111</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7tr9" style="background-color:#fffaf0;"></div> | ||
[[Category: Ke | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Escherichia coli #1/H766]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Pyrococcus furiosus DSM 3638]] | |||
[[Category: Hu C]] | |||
[[Category: Ke A]] | |||
[[Category: Majumdar S]] | |||
[[Category: McLean J]] | |||
[[Category: Nam KH]] | |||
[[Category: Ni D]] | |||
[[Category: Stahlberg H]] | |||
[[Category: Terns M]] | |||