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| Title | Structural basis for regulation of a CBASS-CRISPR-Cas defense island by a transmembrane anti-σ factor and its ECF σ partner. |
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| Journal, issue, pages | Sci Adv, Vol. 10, Issue 43, Page eadp1053, Year 2024 |
| Publish date | Oct 25, 2024 |
Authors | Diego Bernal-Bernal / David Pantoja-Uceda / Jorge Pedro López-Alonso / Alfonso López-Rojo / José Antonio López-Ruiz / Marisa Galbis-Martínez / Borja Ochoa-Lizarralde / Igor Tascón / Montserrat Elías-Arnanz / Iban Ubarretxena-Belandia / S Padmanabhan / ![]() |
| PubMed Abstract | How CRISPR-Cas and cyclic oligonucleotide-based antiphage signaling systems (CBASS) are coordinately deployed against invaders remains unclear. We show that a locus containing two CBASS and one type ...How CRISPR-Cas and cyclic oligonucleotide-based antiphage signaling systems (CBASS) are coordinately deployed against invaders remains unclear. We show that a locus containing two CBASS and one type III-B CRISPR-Cas system, regulated by the transmembrane anti-σ DdvA and its cognate extracytoplasmic function (ECF) σ DdvS, can defend against a phage. Cryo-electron microscopy reveals DdvA-DdvS pairs assemble as arrow-shaped transmembrane dimers. Each DdvA periplasmic domain adopts a separase/craspase-type tetratricopeptide repeat (TPR)-caspase HetF-associated with TPR (TPR-CHAT) architecture with an incomplete His-Cys active site, lacking three α-helices conserved among CHAT domains. Each active site faces the dimer interface, raising the possibility that signal-induced caspase-like DdvA autoproteolysis in trans precedes RseP-mediated intramembrane proteolysis and DdvS release. Nuclear magnetic resonance reveals a DdvA cytoplasmic CHCC-type zinc-bound three-helix bundle that binds to DdvS σ and σ domains, undergoing σ-induced helix extension to trap DdvS. Altogether, we provide structural-mechanistic insights into membrane anti-σ-ECF σ regulation of an antiviral CBASS-CRISPR-Cas defense island. |
External links | Sci Adv / PubMed:39454004 / PubMed Central |
| Methods | EM (single particle) / NMR (solution) |
| Resolution | 2.94 - 3.11 Å |
| Structure data | EMDB-19404, PDB-8rot: EMDB-19543, PDB-8rw5: ![]() PDB-8rlz: |
| Chemicals | ![]() ChemComp-ZN: |
| Source |
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Keywords | TRANSCRIPTION / Membrane antisigma / Zinc-associated antisigma domain / ECF sigma binding domain / Three-helix bundle / SIGNALING PROTEIN / Transmembrane protein / anti-sigma factor / antiviral system / TPR-CHAT |
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myxococcus xanthus (bacteria)
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