8rw5
Symmetry expansion of dimeric transmembrane anti-sigma factor DdvASymmetry expansion of dimeric transmembrane anti-sigma factor DdvA
Structural highlights
Publication Abstract from PubMedHow 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-sigma DdvA and its cognate extracytoplasmic function (ECF) sigma DdvS, can defend Myxococcus xanthus 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 alpha-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 sigma(2) and sigma(4) domains, undergoing sigma(4)-induced helix extension to trap DdvS. Altogether, we provide structural-mechanistic insights into membrane anti-sigma-ECF sigma regulation of an antiviral CBASS-CRISPR-Cas defense island. Structural basis for regulation of a CBASS-CRISPR-Cas defense island by a transmembrane anti-sigma factor and its ECF sigma partner.,Bernal-Bernal D, Pantoja-Uceda D, Lopez-Alonso JP, Lopez-Rojo A, Lopez-Ruiz JA, Galbis-Martinez M, Ochoa-Lizarralde B, Tascon I, Elias-Arnanz M, Ubarretxena-Belandia I, Padmanabhan S Sci Adv. 2024 Oct 25;10(43):eadp1053. doi: 10.1126/sciadv.adp1053. Epub 2024 Oct , 25. PMID:39454004[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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