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6o7b

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Current revision

Crystal structure of Csm1-Csm4 cassette in complex with cA4

Structural highlights

6o7b is a 4 chain structure with sequence from Thermococcus onnurineus, Thermococcus onnurineus NA1 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSM4_THEON 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). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities.[UniProtKB:A0A0A7HGA1] The subunit probably binds to the 5' handle of the crRNA, helping in discrimination between self- and non-self.[UniProtKB:A0A0A7HGA1]

Publication Abstract from PubMed

Target RNA binding to crRNA-bound type III-A CRISPR-Cas multi-subunit Csm surveillance complexes activates cyclic-oligoadenylate (cAn) formation from ATP subunits positioned within the composite pair of Palm domain pockets of the Csm1 subunit. The generated cAn second messenger in turn targets the CARF domain of trans-acting RNase Csm6, triggering its HEPN domain-based RNase activity. We have undertaken cryo-EM studies on multi-subunit Thermococcus onnurineus Csm effector ternary complexes, as well as X-ray studies on Csm1-Csm4 cassette, both bound to substrate (AMPPNP), intermediates (pppAn), and products (cAn), to decipher mechanistic aspects of cAn formation and release. A network of intermolecular hydrogen bond alignments accounts for the observed adenosine specificity, with ligand positioning dictating formation of linear pppAn intermediates and subsequent cAn formation by cyclization. We combine our structural results with published functional studies to highlight mechanistic insights into the role of the Csm effector complex in mediating the cAn signaling pathway.

Second Messenger cA4 Formation within the Composite Csm1 Palm Pocket of Type III-A CRISPR-Cas Csm Complex and Its Release Path.,Jia N, Jones R, Sukenick G, Patel DJ Mol Cell. 2019 Jun 28. pii: S1097-2765(19)30446-0. doi:, 10.1016/j.molcel.2019.06.013. PMID:31326272^[1]

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

References

↑ Jia N, Jones R, Sukenick G, Patel DJ. Second Messenger cA4 Formation within the Composite Csm1 Palm Pocket of Type III-A CRISPR-Cas Csm Complex and Its Release Path. Mol Cell. 2019 Jun 28. pii: S1097-2765(19)30446-0. doi:, 10.1016/j.molcel.2019.06.013. PMID:31326272 doi:http://dx.doi.org/10.1016/j.molcel.2019.06.013

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6o7b"

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 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/CAS10_THEON CAS10_THEON] 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). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities.[UniProtKB:A0A0A7HFE1]  A single-strand deoxyribonuclease (ssDNase) which digests linear and circular ssDNA; has 5'-3' and 3'-5' exonuclease activity as well as a less efficient endonuclease activity. Has a minimal size requirement; 100 nucleotide ssDNA (nt) is more efficiently digested than 50 or 25 nt ssDNA, while 14 nt ssDNA is not cleaved at all. It has no activity on dsDNA or ssRNA.<ref>PMID:25773141</ref>   ssDNase activity is stimulated in the ternary Csm effector complex; binding of cognate target RNA activates the ssDNase, as the target RNA is degraded ssDNA activity decreases.[UniProtKB:A0A0A7HFE1]  When associated with the ternary Csm effector complex (the crRNA, Cas proteins and a cognate target ssRNA) synthesizes cyclic oligoadenylates (cOA) from ATP. cOAs are second messengers that stimulate the ssRNase activity of Csm6, inducing an antiviral state important for defense against invading nucleic acids.[UniProtKB:A0A0A7HFE1]
+[https://www.uniprot.org/uniprot/CSM4_THEON CSM4_THEON] 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). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities.[UniProtKB:A0A0A7HGA1]  The subunit probably binds to the 5' handle of the crRNA, helping in discrimination between self- and non-self.[UniProtKB:A0A0A7HGA1]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6o7b

From Proteopedia

Current revision

Crystal structure of Csm1-Csm4 cassette in complex with cA4

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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