View source for 6mcc


==CryoEM structure of AcrIIA2 homolog in complex with CRISPR-Cas9==
<SX load='6mcc' size='340' side='right' viewer='molstar' caption='[[6mcc]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mcc]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Listeria_phage_lp-101 Listeria phage lp-101] and [http://en.wikipedia.org/wiki/Streptococcus_pyogenes_(serotype_1_/_m1_gas) Streptococcus pyogenes (serotype 1 / m1 gas)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MCC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MCC FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cas9, M1GAS476_0830 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=160490 Streptococcus pyogenes (serotype 1 / M1 GAS)])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6mcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mcc OCA], [http://pdbe.org/6mcc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mcc RCSB], [http://www.ebi.ac.uk/pdbsum/6mcc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mcc ProSAT]</span></td></tr>
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== Function ==
[[http://www.uniprot.org/uniprot/J7M7J1_STRP1 J7M7J1_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). 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; Cas9 is inactive in the absence of the 2 guide RNAs (gRNA). 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.[HAMAP-Rule:MF_01480] 
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== Publication Abstract from PubMed ==
CRISPR-Cas immune systems utilize RNA-guided nucleases to protect bacteria from bacteriophage infection. Bacteriophages have in turn evolved inhibitory "anti-CRISPR" (Acr) proteins, including six inhibitors (AcrIIA1-AcrIIA6) that can block DNA cutting and genome editing by type II-A CRISPR-Cas9 enzymes. We show here that AcrIIA2 and its more potent homolog, AcrIIA2b, prevent Cas9 binding to DNA by occluding protein residues required for DNA binding. Cryo-EM-determined structures of AcrIIA2 or AcrIIA2b bound to S. pyogenes Cas9 reveal a mode of competitive inhibition of DNA binding that is distinct from other known Acrs. Differences in the temperature dependence of Cas9 inhibition by AcrIIA2 and AcrIIA2b arise from differences in both inhibitor structure and the local inhibitor-binding environment on Cas9. These findings expand the natural toolbox for regulating CRISPR-Cas9 genome editing temporally, spatially, and conditionally.

Temperature-Responsive Competitive Inhibition of CRISPR-Cas9.,Jiang F, Liu JJ, Osuna BA, Xu M, Berry JD, Rauch BJ, Nogales E, Bondy-Denomy J, Doudna JA Mol Cell. 2018 Dec 19. pii: S1097-2765(18)30986-9. doi:, 10.1016/j.molcel.2018.11.016. PMID:30595438<ref>PMID:30595438</ref>

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

==See Also==
*[[Endonuclease 3D structures|Endonuclease 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Listeria phage lp-101]]
[[Category: Doudna, J A]]
[[Category: Jiang, F]]
[[Category: Liu, J J]]
[[Category: Acriia2]]
[[Category: Anti-crispr]]
[[Category: Bacteriophage]]
[[Category: Cas9]]
[[Category: Cas9 inhibitor]]
[[Category: Crispr-ca]]
[[Category: Gene editing]]
[[Category: Hydrolase-rna-viral protein complex]]