Your browser doesn't support javascript.
loading
Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.
Lau, Rebecca K; Ye, Qiaozhen; Birkholz, Erica A; Berg, Kyle R; Patel, Lucas; Mathews, Ian T; Watrous, Jeramie D; Ego, Kaori; Whiteley, Aaron T; Lowey, Brianna; Mekalanos, John J; Kranzusch, Philip J; Jain, Mohit; Pogliano, Joe; Corbett, Kevin D.
Afiliación
  • Lau RK; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
  • Ye Q; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Birkholz EA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Berg KR; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Chemistry, University of California, San Diego, La Jolla, CA, USA.
  • Patel L; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Mathews IT; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Watrous JD; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Ego K; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Whiteley AT; Department of Microbiology, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lowey B; Department of Microbiology, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Mekalanos JJ; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Kranzusch PJ; Department of Microbiology, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Jain M; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Pogliano J; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
  • Corbett KD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Chemistry, University of California, San Diego, La Jolla, CA, USA; Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, CA, USA. Electronic address: kcorbett@ucsd.edu.
Mol Cell ; 77(4): 723-733.e6, 2020 02 20.
Article en En | MEDLINE | ID: mdl-31932164
ABSTRACT
Bacteria 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.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Desoxirribonucleasa I / Escherichia coli Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Desoxirribonucleasa I / Escherichia coli Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos