5xn4: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5xn4 is ~~ON HOLD until Paper~~ Publication

==Anti-CRISPR protein AcrIIA4==

== Structural highlights ==

<table><tr><td colspan='2'>[[5xn4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XN4 FirstGlance]. <br>

</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xn4 OCA], [http://pdbe.org/5xn4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xn4 RCSB], [http://www.ebi.ac.uk/pdbsum/5xn4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xn4 ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

The bacterial CRISPR-Cas system provides adaptive immunity against invading phages. Cas9, an RNA-guided endonuclease, specifically cleaves target DNA substrates and constitutes a well-established platform for genome editing. Recently, anti-CRISPR (Acr) proteins that inhibit Cas9 have been discovered, promising a useful off-switch for Cas9 to avoid undesirable off-target effects. Here, we report the solution structure and dynamics of Listeria monocytogenes AcrIIA4 that inhibits Streptococcus pyogenes Cas9 (SpyCas9). AcrIIA4 forms a compact monomeric alphabetabetabetaalphaalpha fold comprising three antiparallel beta strands flanked by three alpha-helices and a short 310-helix. AcrIIA4 exhibits distinct backbone dynamics in fast and slow timescales at loop regions that form interaction surfaces for SpyCas9. In particular, the beta1-beta2 loop that binds to the RuvC domain of SpyCas9 is highly mobile, and the beta1-beta2 and alpha2-alpha3 loops that bind to the RuvC and C-terminal domains of SpyCas9, respectively, undergoes conformational exchanges in microsecond-to-millisecond time scales. AcrIIA4 binds to apo-SpyCas9 with KD ~4.8 muM, which compares to KD ~0.6 nM for AcrIIA4 binding to sgRNA-bound SpyCas9. Since the binary complex between AcrIIA4 and SpyCas9 does not compete with the target DNA binding, it can effectively disable the Cas9 nuclease activity by forming a tight ternary complex in the presence of sgRNA.

~~Authors: Suh~~, ~~J.-Y~~., Kim, I.

Solution structure and dynamics of anti-CRISPR AcrIIA4, the Cas9 inhibitor.,Kim I, Jeong M, Ka D, Han M, Kim NK, Bae E, Suh JY Sci Rep. 2018 Mar 1;8(1):3883. doi: 10.1038/s41598-018-22177-0. PMID:29497118<ref>PMID:29497118</ref>

~~Description~~: ~~Anti-CRISPR protein AcrIIA4~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

~~[[Category: Unreleased Structures]]~~

</div>

~~[[Category: Suh, J.-Y]]~~

== References ==

__TOC__

</StructureSection>

[[Category: Kim, I]]

[[Category: Suh, J Y]]

[[Category: Cas9 inhibitor]]

[[Category: Hydrolase inhibitor]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5xn4 is ON HOLD  until Paper Publication
+==Anti-CRISPR protein AcrIIA4==
+<StructureSection load='5xn4' size='340' side='right' caption='[[5xn4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5xn4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XN4 FirstGlance]. <br>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xn4 OCA], [http://pdbe.org/5xn4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xn4 RCSB], [http://www.ebi.ac.uk/pdbsum/5xn4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xn4 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The bacterial CRISPR-Cas system provides adaptive immunity against invading phages. Cas9, an RNA-guided endonuclease, specifically cleaves target DNA substrates and constitutes a well-established platform for genome editing. Recently, anti-CRISPR (Acr) proteins that inhibit Cas9 have been discovered, promising a useful off-switch for Cas9 to avoid undesirable off-target effects. Here, we report the solution structure and dynamics of Listeria monocytogenes AcrIIA4 that inhibits Streptococcus pyogenes Cas9 (SpyCas9). AcrIIA4 forms a compact monomeric alphabetabetabetaalphaalpha fold comprising three antiparallel beta strands flanked by three alpha-helices and a short 310-helix. AcrIIA4 exhibits distinct backbone dynamics in fast and slow timescales at loop regions that form interaction surfaces for SpyCas9. In particular, the beta1-beta2 loop that binds to the RuvC domain of SpyCas9 is highly mobile, and the beta1-beta2 and alpha2-alpha3 loops that bind to the RuvC and C-terminal domains of SpyCas9, respectively, undergoes conformational exchanges in microsecond-to-millisecond time scales. AcrIIA4 binds to apo-SpyCas9 with KD ~4.8 muM, which compares to KD ~0.6 nM for AcrIIA4 binding to sgRNA-bound SpyCas9. Since the binary complex between AcrIIA4 and SpyCas9 does not compete with the target DNA binding, it can effectively disable the Cas9 nuclease activity by forming a tight ternary complex in the presence of sgRNA.
-Authors: Suh, J.-Y., Kim, I.
+Solution structure and dynamics of anti-CRISPR AcrIIA4, the Cas9 inhibitor.,Kim I, Jeong M, Ka D, Han M, Kim NK, Bae E, Suh JY Sci Rep. 2018 Mar 1;8(1):3883. doi: 10.1038/s41598-018-22177-0. PMID:29497118<ref>PMID:29497118</ref>
-Description: Anti-CRISPR protein AcrIIA4
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Suh, J.-Y]]
+<div class="pdbe-citations 5xn4" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Kim, I]]
+[[Category: Suh, J Y]]
+[[Category: Cas9 inhibitor]]
+[[Category: Hydrolase inhibitor]]