7una
From Proteopedia
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== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/CAP12_SPHFK CAP12_SPHFK]] CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type I-D(GG) CBASS system (PubMed:32839535).<ref>PMID:32839535</ref> <ref>PMID:32877915</ref> The effector protein for this CBASS system. Upon activation by c-di-GMP forms filaments which hydrolyze NAD(+); filament formation is required for enzyme activation. Induction in an E.coli strain that synthesizes c-di-GMP leads to significant growth inhibition. Binds c-di-GMP and 3'3'-cGAMP (3'3'-cyclic GMP-AMP), but not c-di-AMP, 2'3'-cGAMP or cUMP-AMP.<ref>PMID:32877915</ref> | [[https://www.uniprot.org/uniprot/CAP12_SPHFK CAP12_SPHFK]] CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type I-D(GG) CBASS system (PubMed:32839535).<ref>PMID:32839535</ref> <ref>PMID:32877915</ref> The effector protein for this CBASS system. Upon activation by c-di-GMP forms filaments which hydrolyze NAD(+); filament formation is required for enzyme activation. Induction in an E.coli strain that synthesizes c-di-GMP leads to significant growth inhibition. Binds c-di-GMP and 3'3'-cGAMP (3'3'-cyclic GMP-AMP), but not c-di-AMP, 2'3'-cGAMP or cUMP-AMP.<ref>PMID:32877915</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Stimulator of interferon genes (STING) is an antiviral signalling protein that is broadly conserved in both innate immunity in animals and phage defence in prokaryotes(1-4). Activation of STING requires its assembly into an oligomeric filament structure through binding of a cyclic dinucleotide(4-13), but the molecular basis of STING filament assembly and extension remains unknown. Here we use cryogenic electron microscopy to determine the structure of the active Toll/interleukin-1 receptor (TIR)-STING filament complex from a Sphingobacterium faecium cyclic-oligonucleotide-based antiphage signalling system (CBASS) defence operon. Bacterial TIR-STING filament formation is driven by STING interfaces that become exposed on high-affinity recognition of the cognate cyclic dinucleotide signal c-di-GMP. Repeating dimeric STING units stack laterally head-to-head through surface interfaces, which are also essential for human STING tetramer formation and downstream immune signalling in mammals(5). The active bacterial TIR-STING structure reveals further cross-filament contacts that brace the assembly and coordinate packing of the associated TIR NADase effector domains at the base of the filament to drive NAD(+) hydrolysis. STING interface and cross-filament contacts are essential for cell growth arrest in vivo and reveal a stepwise mechanism of activation whereby STING filament assembly is required for subsequent effector activation. Our results define the structural basis of STING filament formation in prokaryotic antiviral signalling. | ||
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| + | Cryo-EM structure of an active bacterial TIR-STING filament complex.,Morehouse BR, Yip MCJ, Keszei AFA, McNamara-Bordewick NK, Shao S, Kranzusch PJ Nature. 2022 Jul 20. pii: 10.1038/s41586-022-04999-1. doi:, 10.1038/s41586-022-04999-1. PMID:35859168<ref>PMID:35859168</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7una" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 18:58, 7 September 2022
SfSTING with cGAMP (masked)
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