6rja: Difference between revisions

Latest revision as of 10:12, 22 May 2024

Cryo-EM structure of St1Cas9-sgRNA-tDNA20-AcrIIA6 dimeric assembly.

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Structural highlights

6rja is a 8 chain structure with sequence from Streptococcus phage D1811, Streptococcus thermophilus, Streptococcus thermophilus LMD-9 and Streptococcus virus 2972. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A2U7VKE8_9CAUD

Publication Abstract from PubMed

In the arms race against bacteria, bacteriophages have evolved diverse anti-CRISPR proteins (Acrs) that block CRISPR-Cas immunity. Acrs play key roles in the molecular coevolution of bacteria with their predators, use a variety of mechanisms of action, and provide tools to regulate Cas-based genome manipulation. Here, we present structural and functional analyses of AcrIIA6, an Acr from virulent phages, exploring its unique anti-CRISPR action. Our cryo-EM structures and functional data of AcrIIA6 binding to Streptococcus thermophilus Cas9 (St1Cas9) show that AcrIIA6 acts as an allosteric inhibitor and induces St1Cas9 dimerization. AcrIIA6 reduces St1Cas9 binding affinity for DNA and prevents DNA binding within cells. The PAM and AcrIIA6 recognition sites are structurally close and allosterically linked. Mechanistically, AcrIIA6 affects the St1Cas9 conformational dynamics associated with PAM binding. Finally, we identify a natural St1Cas9 variant resistant to AcrIIA6 illustrating Acr-driven mutational escape and molecular diversification of Cas9 proteins.

Cas9 Allosteric Inhibition by the Anti-CRISPR Protein AcrIIA6.,Fuchsbauer O, Swuec P, Zimberger C, Amigues B, Levesque S, Agudelo D, Duringer A, Chaves-Sanjuan A, Spinelli S, Rousseau GM, Velimirovic M, Bolognesi M, Roussel A, Cambillau C, Moineau S, Doyon Y, Goulet A Mol Cell. 2019 Sep 26. pii: S1097-2765(19)30697-5. doi:, 10.1016/j.molcel.2019.09.012. PMID:31604602^[1]

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

References

↑ Fuchsbauer O, Swuec P, Zimberger C, Amigues B, Levesque S, Agudelo D, Duringer A, Chaves-Sanjuan A, Spinelli S, Rousseau GM, Velimirovic M, Bolognesi M, Roussel A, Cambillau C, Moineau S, Doyon Y, Goulet A. Cas9 Allosteric Inhibition by the Anti-CRISPR Protein AcrIIA6. Mol Cell. 2019 Sep 26. pii: S1097-2765(19)30697-5. doi:, 10.1016/j.molcel.2019.09.012. PMID:31604602 doi:https://dx.doi.org/10.1016/j.molcel.2019.09.012

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OCA

[1] Fuchsbauer O, Swuec P, Zimberger C, Amigues B, Levesque S, Agudelo D, Duringer A, Chaves-Sanjuan A, Spinelli S, Rousseau GM, Velimirovic M, Bolognesi M, Roussel A, Cambillau C, Moineau S, Doyon Y, Goulet A. Cas9 Allosteric Inhibition by the Anti-CRISPR Protein AcrIIA6. Mol Cell. 2019 Sep 26. pii: S1097-2765(19)30697-5. doi:, 10.1016/j.molcel.2019.09.012. PMID:31604602 doi:https://dx.doi.org/10.1016/j.molcel.2019.09.012

[1]

@@ Line 3: / Line 3: @@
 <SX load='6rja' size='340' side='right' viewer='molstar' caption='[[6rja]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rja]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Streptococcus_phage_d1811 Streptococcus phage d1811]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RJA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rja]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_phage_D1811 Streptococcus phage D1811], [https://en.wikipedia.org/wiki/Streptococcus_thermophilus Streptococcus thermophilus], [https://en.wikipedia.org/wiki/Streptococcus_thermophilus_LMD-9 Streptococcus thermophilus LMD-9] and [https://en.wikipedia.org/wiki/Streptococcus_virus_2972 Streptococcus virus 2972]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RJA FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6rj9|6rj9]], [[6rjd|6rjd]], [[6rjg|6rjg]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">D1811_026 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2108111 Streptococcus phage D1811]), cas9-1, csn1, STER_0709 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2108111 Streptococcus phage D1811])</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=6rja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rja OCA], [https://pdbe.org/6rja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rja RCSB], [https://www.ebi.ac.uk/pdbsum/6rja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rja ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CAS9A_STRTD CAS9A_STRTD]] 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 (By similarity). Cuts target DNA when Cas9 and gRNAs are mixed.[HAMAP-Rule:MF_01480]<ref>PMID:24270795</ref>
+[https://www.uniprot.org/uniprot/A0A2U7VKE8_9CAUD A0A2U7VKE8_9CAUD]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 </SX>
 [[Category: Large Structures]]
-[[Category: Streptococcus phage d1811]]
+[[Category: Streptococcus phage D1811]]
-[[Category: Cambillau, C]]
+[[Category: Streptococcus thermophilus]]
-[[Category: Chaves-Sanjuan, A]]
+[[Category: Streptococcus thermophilus LMD-9]]
-[[Category: Goulet, A]]
+[[Category: Streptococcus virus 2972]]
-[[Category: Anti-crispr protein]]
+[[Category: Cambillau C]]
-[[Category: Bacteriophage]]
+[[Category: Chaves-Sanjuan A]]
-[[Category: Crispr-cas9]]
+[[Category: Goulet A]]
-[[Category: Hydrolase]]
-[[Category: St1cas9]]
-[[Category: Streptococcus thermophilus cas9]]

6rja: Difference between revisions

Latest revision as of 10:12, 22 May 2024

Cryo-EM structure of St1Cas9-sgRNA-tDNA20-AcrIIA6 dimeric assembly.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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