학술논문
Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides.
Document Type
Academic Journal
Author
Rechkoblit O; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. olga.rechkoblit@mssm.edu.; Sciaky D; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Kreitler DF; Center for BioMolecular Structure NSLS‑II, Brookhaven National Laboratory, Upton, NY, USA.; Buku A; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Kottur J; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Antiviral Research, Institute of Advanced Virology, Thiruvananthapuram, India.; Aggarwal AK; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. aneel.aggarwal@mssm.edu.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101186374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-9985 (Electronic) Linking ISSN: 15459985 NLM ISO Abbreviation: Nat Struct Mol Biol Subsets: MEDLINE
Subject
Language
English
Abstract
The bacterial cyclic oligonucleotide-based antiphage signaling system (CBASS) is similar to the cGAS-STING system in humans, containing an enzyme that synthesizes a cyclic nucleotide on viral infection and an effector that senses the second messenger for the antiviral response. Cap5, containing a SAVED domain coupled to an HNH DNA endonuclease domain, is the most abundant CBASS effector, yet the mechanism by which it becomes activated for cell killing remains unknown. We present here high-resolution structures of full-length Cap5 from Pseudomonas syringae (Ps) with second messengers. The key to PsCap5 activation is a dimer-to-tetramer transition, whereby the binding of second messenger to dimer triggers an open-to-closed transformation of the SAVED domains, furnishing a surface for assembly of the tetramer. This movement propagates to the HNH domains, juxtaposing and converting two HNH domains into states for DNA destruction. These results show how Cap5 effects bacterial cell suicide and we provide proof-in-principle data that the CBASS can be extrinsically activated to limit bacterial infections.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)