6w11
From Proteopedia
The structure of Sulfolobus solfataricus Csa3 in complex with cyclic tetraadenylate (cA4)
Structural highlights
FunctionCSA3_SACS2 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) (By similarity). Publication Abstract from PubMedCsa3 family transcription factors are ancillary CRISPR-associated proteins composed of N-terminal CARF domains and C-terminal winged helix-turn-helix domains. The activity of Csa3 transcription factors is thought to be controlled by cyclic oligoadenyate (cOA) second messengers produced by type III CRISPR-Cas surveillance complexes. Here we show that Saccharolobus solfataricus Csa3a recognizes cyclic tetra-adenylate (cA(4)) and that Csa3a lacks self-regulating "ring nuclease" activity present in some other CARF domain proteins. The crystal structure of the Csa3a/cA4 complex was also determined and the structural and thermodynamic basis for cA(4) recognition are described, as are conformational changes in Csa3a associated with cA(4) binding. We also characterized the effect of cA(4) on recognition of putative DNA binding sites. Csa3a binds to putative promoter sequences in a nonspecific, cooperative and cA(4)-independent manner, suggesting a more complex mode of transcriptional regulation. We conclude the Csa3a/cA(4) interaction represents a nexus between the type I and type III CRISPR-Cas systems present in S. solfataricus, and discuss the role of the Csa3/cA(4) interaction in coordinating different arms of this integrated class 1 immune system to mount a synergistic, highly orchestrated immune response. Cyclic Tetra-Adenylate (cA(4)) Recognition by Csa3; Implications for an Integrated Class 1 CRISPR-Cas Immune Response in Saccharolobus solfataricus.,Charbonneau AA, Eckert DM, Gauvin CC, Lintner NG, Lawrence CM Biomolecules. 2021 Dec 9;11(12):1852. doi: 10.3390/biom11121852. PMID:34944496[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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