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| | <StructureSection load='6vm6' size='340' side='right'caption='[[6vm6]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6vm6' size='340' side='right'caption='[[6vm6]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vm6]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_sp._atcc_27244 Acinetobacter sp. atcc 27244]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VM6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VM6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vm6]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_sp._ATCC_27244 Acinetobacter sp. ATCC 27244] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VM6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMPREF0023_0548 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=525244 Acinetobacter sp. ATCC 27244])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vm6 OCA], [http://pdbe.org/6vm6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vm6 RCSB], [http://www.ebi.ac.uk/pdbsum/6vm6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vm6 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vm6 OCA], [https://pdbe.org/6vm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vm6 RCSB], [https://www.ebi.ac.uk/pdbsum/6vm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vm6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/CAP4_ACIS2 CAP4_ACIS2] 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 II-C(AAAA) CBASS system (PubMed:32839535).<ref>PMID:32839535</ref> <ref>PMID:32544385</ref> Binds cyclic nucleotide second messengers (synthesized by CdnD, the cognate CD-NTase in the CBASS operon). Ligand binding activates it to endonucleolytically degrade dsDNA to approximately 6 bp length fragments, with a preference for 5'-C or 5'-G cleavage site. The minor product of CdnD is the activating nucleotide; also binds the major product (2',3',3'-cyclic AMP-AMP-AMP) but is not activated by it. Only binds DNA in the presence of ligand. Is not activated by c-di-AMP, c-di-GMP, 3'3'-cyclic GMP-AMP (3'3'-cGAMP) or 3',3',3'-cyclic AMP-AMP-GMP.<ref>PMID:32544385</ref> |
| - | cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated protein 4 (Cap4) as a founding member of a diverse family of >2,000 bacterial receptors that respond to CD-NTase signals. Structures of Cap4 reveal a promiscuous DNA endonuclease domain activated through ligand-induced oligomerization. Oligonucleotide recognition occurs through an appended SAVED domain that is an unexpected fusion of two CRISPR-associated Rossman fold (CARF) subunits co-opted from type III CRISPR immunity. Like a lock and key, SAVED effectors exquisitely discriminate 2'-5'- and 3'-5'-linked bacterial cyclic oligonucleotide signals and enable specific recognition of at least 180 potential nucleotide second messenger species. Our results reveal SAVED CARF family proteins as major nucleotide second messenger receptors in CBASS and CRISPR immune defense and extend the importance of linkage specificity beyond mammalian cGAS-STING signaling.
| + | |
| - | | + | |
| - | CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection.,Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385<ref>PMID:32544385</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6vm6" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acinetobacter sp. atcc 27244]] | + | [[Category: Acinetobacter sp. ATCC 27244]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Antine, S P]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Cabrera, V]] | + | [[Category: Antine SP]] |
| - | [[Category: Keszei, A F.A]] | + | [[Category: Cabrera V]] |
| - | [[Category: Kranzusch, P J]] | + | [[Category: Keszei AFA]] |
| - | [[Category: Lee, A S.Y]] | + | [[Category: Kranzusch PJ]] |
| - | [[Category: Lowey, B]] | + | [[Category: Lee ASY]] |
| - | [[Category: Mekalanos, J J]] | + | [[Category: Lowey B]] |
| - | [[Category: Morehouse, B R]] | + | [[Category: Mekalanos JJ]] |
| - | [[Category: Schwede, F]] | + | [[Category: Morehouse BR]] |
| - | [[Category: Shao, S]] | + | [[Category: Schwede F]] |
| - | [[Category: Whiteley, A T]] | + | [[Category: Shao S]] |
| - | [[Category: Carf]]
| + | [[Category: Whiteley AT]] |
| - | [[Category: Duf4297]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nuclease]]
| + | |
| - | [[Category: Phage immunity]]
| + | |
| - | [[Category: Saved]]
| + | |
| Structural highlights
Function
CAP4_ACIS2 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 II-C(AAAA) CBASS system (PubMed:32839535).[1] [2] Binds cyclic nucleotide second messengers (synthesized by CdnD, the cognate CD-NTase in the CBASS operon). Ligand binding activates it to endonucleolytically degrade dsDNA to approximately 6 bp length fragments, with a preference for 5'-C or 5'-G cleavage site. The minor product of CdnD is the activating nucleotide; also binds the major product (2',3',3'-cyclic AMP-AMP-AMP) but is not activated by it. Only binds DNA in the presence of ligand. Is not activated by c-di-AMP, c-di-GMP, 3'3'-cyclic GMP-AMP (3'3'-cGAMP) or 3',3',3'-cyclic AMP-AMP-GMP.[3]
References
- ↑ Millman A, Melamed S, Amitai G, Sorek R. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat Microbiol. 2020 Dec;5(12):1608-1615. doi: 10.1038/s41564-020-0777-y. Epub, 2020 Aug 24. PMID:32839535 doi:http://dx.doi.org/10.1038/s41564-020-0777-y
- ↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019
- ↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019
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