View source for 6p7p


==Structure of E. coli MS115-1 NucC, cAAA-bound form==
<StructureSection load='6p7p' size='340' side='right'caption='[[6p7p]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6p7p]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_MS_115-1 Escherichia coli MS 115-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P7P FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.665&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=6p7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p7p OCA], [https://pdbe.org/6p7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p7p RCSB], [https://www.ebi.ac.uk/pdbsum/6p7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p7p ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NUCC_ECOM1 NUCC_ECOM1] 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 III-C(AAA) CBASS system (PubMed:32839535).<ref>PMID:31932165</ref> <ref>PMID:32839535</ref>   A cyclic nucleotide-activated dsDNase. In the presence of 3',3',3'-cyclic AMP-AMP-AMP (cAAA), and to a lesser extent 3',3',3'-cyclic AMP-AMP-GMP (cAAG) and cyclic-di-AMP (c-di-AMP), endonucleolytically degrades dsDNA (PubMed:31932165, PubMed:31932164). Binds one cAAA in a pocket on one surface of the trimer; cAAA binding promotes hexamerization, which is necessary for nuclease activation. Also binds c-diAMP or linear di-AMP with lower affinity. The nuclease digests dsDNA to about 50 bp lengths with a 2-base 3' overhang and a consensus recognition site of 5'-Axx|T-3'. DNA has been modeled to contact a pair of juxtaposed active sites (one from each layer of the hexamer), accounting for cleavage on both strands and the 2-base overhang (PubMed:31932164).<ref>PMID:31932164</ref> <ref>PMID:31932165</ref>   Protects E.coli strain JP313 against bacteriophage lambda cI- infection. When the cdnC-cap7-cap6-nucC operon is transformed into a susceptible strain it confers bacteriophage immunity. Mutations in the sensor (Cap7 also called HORMA) or effector proteins (CdnC, NucC) but not the disassembly protein (Cap6 also called Trip13) no longer confer immunity. The presence of the intact operon leads to culture collapse and cell death which occurs before the phage has finished its replication cycle, thus protecting non-infected bacteria by aborting the phage infection and preventing its propagation.<ref>PMID:31932164</ref> <ref>PMID:31932165</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer. Binding of NucC trimers to a cyclic tri-adenylate second messenger promotes assembly of a NucC homohexamer competent for non-specific double-strand DNA cleavage. In infected cells, NucC activation leads to complete destruction of the bacterial chromosome, causing cell death prior to completion of phage replication. In addition to CBASS systems, we identify NucC homologs in over 30 type III CRISPR/Cas systems, where they likely function as accessory nucleases activated by cyclic oligoadenylate second messengers synthesized by these systems' effector complexes.

Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.,Lau RK, Ye Q, Birkholz EA, Berg KR, Patel L, Mathews IT, Watrous JD, Ego K, Whiteley AT, Lowey B, Mekalanos JJ, Kranzusch PJ, Jain M, Pogliano J, Corbett KD Mol Cell. 2020 Jan 6. pii: S1097-2765(19)30923-2. doi:, 10.1016/j.molcel.2019.12.010. PMID:31932164<ref>PMID:31932164</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6p7p" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli MS 115-1]]
[[Category: Large Structures]]
[[Category: Berg KR]]
[[Category: Corbett KD]]
[[Category: Lau RK]]
[[Category: Ye Q]]