6uxf | pdb_00006uxf
Structure of V. metoecus NucC, hexamer form
Structural highlights
FunctionNUCC_VIBMT 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).[1] A cyclic nucleotide-activated dsDNase. In the presence of 3',3',3'-cyclic AMP-AMP-AMP (cAAA), and to a much lesser extent 3',3',3'-cyclic AMP-AMP-GMP (cAAG) and cyclic-di-AMP (c-di-AMP), endonucleolytically degrades dsDNA. The nuclease digests dsDNA to about 50 bp lengths. Not stimulated by cGAMP or linear di-AMP (PubMed:31932164). DNA has been modeled to contact a pair of juxtaposed active sites (one from each layer of the hexamer), accounting for cleavage on both strands (By similarity).[UniProtKB:D7Y2H5][2] Publication Abstract from PubMedBacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer. Binding of NucC trimers to a cyclic tri-adenylate second messenger promotes assembly of a NucC homohexamer competent for non-specific double-strand DNA cleavage. In infected cells, NucC activation leads to complete destruction of the bacterial chromosome, causing cell death prior to completion of phage replication. In addition to CBASS systems, we identify NucC homologs in over 30 type III CRISPR/Cas systems, where they likely function as accessory nucleases activated by cyclic oligoadenylate second messengers synthesized by these systems' effector complexes. Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.,Lau RK, Ye Q, Birkholz EA, Berg KR, Patel L, Mathews IT, Watrous JD, Ego K, Whiteley AT, Lowey B, Mekalanos JJ, Kranzusch PJ, Jain M, Pogliano J, Corbett KD Mol Cell. 2020 Jan 6. pii: S1097-2765(19)30923-2. doi:, 10.1016/j.molcel.2019.12.010. PMID:31932164[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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