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Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages.
Carabias, Arturo; Camara-Wilpert, Sarah; Mestre, Mario Rodríguez; Lopéz-Méndez, Blanca; Hendriks, Ivo A; Zhao, Ruiliang; Pape, Tillmann; Fuglsang, Anders; Luk, Sean Hoi-Ching; Nielsen, Michael L; Pinilla-Redondo, Rafael; Montoya, Guillermo.
Afiliación
  • Carabias A; Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: arturo.cdr@cpr.ku.dk.
  • Camara-Wilpert S; Section of Microbiology, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
  • Mestre MR; Section of Microbiology, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
  • Lopéz-Méndez B; Protein Purification and Characterization Facility, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Hendriks IA; Proteomics Department, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Zhao R; Section of Microbiology, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
  • Pape T; Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Core Facility for Integrated Microscopy (CFIM), Faculty of Health and Medical Sciences, University of C
  • Fuglsang A; Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • Luk SH; Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • Nielsen ML; Proteomics Department, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Pinilla-Redondo R; Section of Microbiology, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: rafael.pinilla@bio.ku.dk.
  • Montoya G; Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Electronic address: guillermo.montoya@cpr.ku.dk.
Mol Cell ; 84(11): 2185-2202.e12, 2024 Jun 06.
Article en En | MEDLINE | ID: mdl-38788717
ABSTRACT
Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD+ during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD+ hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector's toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr's pivotal role in immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Microscopía por Crioelectrón / NAD Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Microscopía por Crioelectrón / NAD Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos