6o56
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6o56 is ON HOLD Authors: Newton, J.C., Lisi, G.P., Jogl, G. Description: HNH Nuclease from S. pyogenes Cas9 Category: Unreleased Structures [[C...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==HNH Nuclease from S. pyogenes Cas9== | |
| + | <StructureSection load='6o56' size='340' side='right'caption='[[6o56]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6o56]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_serotype_M1 Streptococcus pyogenes serotype M1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O56 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=6o56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o56 OCA], [https://pdbe.org/6o56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o56 RCSB], [https://www.ebi.ac.uk/pdbsum/6o56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o56 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CAS9_STRP1 CAS9_STRP1] CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA) (Probable). In type II CRISPR systems correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and this protein. The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Subsequently Cas9/crRNA/tracrRNA endonucleolytically cleaves linear or circular dsDNA target complementary to the spacer. The target strand not complementary to crRNA is first cut endonucleolytically, then trimmed by 3'-5' exonucleolytically. DNA-binding requires protein and both RNA species. Cas9 probably recognizes a short motif in the CRISPR repeat sequences (the PAM or protospacer adjacent motif) to help distinguish self versus nonself.<ref>PMID:21455174</ref> <ref>PMID:22745249</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | CRISPR-Cas9 is a widely employed genome-editing tool with functionality reliant on the ability of the Cas9 endonuclease to introduce site-specific breaks in double-stranded DNA. In this system, an intriguing allosteric communication has been suggested to control its DNA cleavage activity through flexibility of the catalytic HNH domain. Here, solution NMR experiments and a novel Gaussian-accelerated molecular dynamics (GaMD) simulation method are used to capture the structural and dynamic determinants of allosteric signaling within the HNH domain. We reveal the existence of a millisecond time scale dynamic pathway that spans HNH from the region interfacing the adjacent RuvC nuclease and propagates up to the DNA recognition lobe in full-length CRISPR-Cas9. These findings reveal a potential route of signal transduction within the CRISPR-Cas9 HNH nuclease, advancing our understanding of the allosteric pathway of activation. Further, considering the role of allosteric signaling in the specificity of CRISPR-Cas9, this work poses the mechanistic basis for novel engineering efforts aimed at improving its genome-editing capability. | ||
| - | + | Allosteric Motions of the CRISPR-Cas9 HNH Nuclease Probed by NMR and Molecular Dynamics.,East KW, Newton JC, Morzan UN, Narkhede YB, Acharya A, Skeens E, Jogl G, Batista VS, Palermo G, Lisi GP J Am Chem Soc. 2020 Jan 9. doi: 10.1021/jacs.9b10521. PMID:31885264<ref>PMID:31885264</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6o56" style="background-color:#fffaf0;"></div> |
| - | [[Category: Jogl | + | |
| - | [[Category: Lisi | + | ==See Also== |
| + | *[[Endonuclease 3D structures|Endonuclease 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Streptococcus pyogenes serotype M1]] | ||
| + | [[Category: Jogl G]] | ||
| + | [[Category: Lisi GP]] | ||
| + | [[Category: Newton JC]] | ||
Current revision
HNH Nuclease from S. pyogenes Cas9
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