6kc0

Structural highlights

Function

CAS10_MYCTU 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 (Probable). This CRISPR-Cas system protects bacteria against transformation with plasmids containing DNA homologous to its spacer regions (PubMed:29979631).^{[1] [2]} This subunit is a single-strand-specific deoxyribonuclease (ssDNase) which digests both linear and circular ssDNA; it has both exo- and endonuclease activity.[UniProtKB:B6YWB8] 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]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.^[3] 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]

References

1. ↑ Wei W, Zhang S, Fleming J, Chen Y, Li Z, Fan S, Liu Y, Wang W, Wang T, Liu Y, Ren B, Wang M, Jiao J, Chen Y, Zhou Y, Zhou Y, Gu S, Zhang X, Wan L, Chen T, Zhou L, Chen Y, Zhang XE, Li C, Zhang H, Bi L. Mycobacterium tuberculosis type III-A CRISPR/Cas system crRNA and its maturation have atypical features. FASEB J. 2019 Jan;33(1):1496-1509. PMID:29979631 doi:10.1096/fj.201800557RR
2. ↑ Wei W, Zhang S, Fleming J, Chen Y, Li Z, Fan S, Liu Y, Wang W, Wang T, Liu Y, Ren B, Wang M, Jiao J, Chen Y, Zhou Y, Zhou Y, Gu S, Zhang X, Wan L, Chen T, Zhou L, Chen Y, Zhang XE, Li C, Zhang H, Bi L. Mycobacterium tuberculosis type III-A CRISPR/Cas system crRNA and its maturation have atypical features. FASEB J. 2019 Jan;33(1):1496-1509. PMID:29979631 doi:10.1096/fj.201800557RR
3. ↑ Jung TY, An Y, Park KH, Lee MH, Oh BH, Woo E. Crystal Structure of the Csm1 Subunit of the Csm Complex and Its Single-Stranded DNA-Specific Nuclease Activity. Structure. 2015 Mar 3. pii: S0969-2126(15)00045-3. doi:, 10.1016/j.str.2015.01.021. PMID:25773141 doi:http://dx.doi.org/10.1016/j.str.2015.01.021
4. ↑ Zhang S, Li T, Huo Y, Yang J, Fleming J, Shi M, Wang Y, Wei W, Gu S, Bi L, Jiang T, Zhang H. Mycobacterium tuberculosis CRISPR/Cas system Csm1 holds clues to the evolutionary relationship between DNA polymerase and cyclase activity. Int J Biol Macromol. 2021 Feb 15;170:140-149. PMID:33352158 doi:10.1016/j.ijbiomac.2020.12.014