View source for 6jdx


==Crystal structure of AcrIIC2 dimer in complex with partial Nme1Cas9 preprocessed with protease alpha-Chymotrypsin==
<StructureSection load='6jdx' size='340' side='right'caption='[[6jdx]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jdx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_8013 Neisseria meningitidis 8013]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JDX 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6jdx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jdx OCA], [https://pdbe.org/6jdx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jdx RCSB], [https://www.ebi.ac.uk/pdbsum/6jdx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jdx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAS9_NEIM8 CAS9_NEIM8] 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). In type II CRISPR systems correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and this protein, although RNase 3 is not required for 5'-processing of crRNA in this strain. Cas9/crRNA/tracrRNA endonucleolytically cleaves linear or circular dsDNA target complementary to the spacer; Cas9 is inactive in the absence of the 2 guide RNAs (gRNA, PubMed:23940360). Cas9 recognizes the protospacer adjacent motif (PAM) in the CRISPR repeat sequences to help distinguish self versus nonself, as targets within the bacterial CRISPR locus do not have PAMs. PAM recognition is also required for catalytic activity. Plasmids containing sequences homologous to endogenous spacer elements and that have flanking PAM consensus sequences cannot transform this strain unless the cas9 gene is disrupted or critical residues of Cas9 are mutated.<ref>PMID:23706818</ref> <ref>PMID:23940360</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CRISPR-Cas adaptive immune systems function to protect bacteria from invasion by foreign genetic elements. The CRISPR-Cas9 system has been widely adopted as a powerful genome-editing tool, and phage-encoded inhibitors, known as anti-CRISPRs, offer a means of regulating its activity. Here, we report the crystal structures of anti-CRISPR protein AcrIIC2Nme alone and in complex with Nme1Cas9. We demonstrate that AcrIIC2Nme inhibits Cas9 through interactions with the positively charged bridge helix, thereby preventing sgRNA loading. In vivo phage plaque assays and in vitro DNA cleavage assays show that AcrIIC2Nme mediates its activity through a large electronegative surface. This work shows that anti-CRISPR activity can be mediated through the inhibition of Cas9 complex assembly.

Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2.,Thavalingam A, Cheng Z, Garcia B, Huang X, Shah M, Sun W, Wang M, Harrington L, Hwang S, Hidalgo-Reyes Y, Sontheimer EJ, Doudna J, Davidson AR, Moraes TF, Wang Y, Maxwell KL Nat Commun. 2019 Jun 26;10(1):2806. doi: 10.1038/s41467-019-10577-3. PMID:31243272<ref>PMID:31243272</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jdx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Endonuclease 3D structures|Endonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria meningitidis 8013]]
[[Category: Cheng Z]]
[[Category: Huang X]]
[[Category: Sun W]]
[[Category: Wang Y]]