View source for 8btp


==Helical structure of BcThsA in complex with 1''-3'gc(etheno)ADPR==
<StructureSection load='8btp' size='340' side='right'caption='[[8btp]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8btp]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus_MSX-D12 Bacillus cereus MSX-D12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BTP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ENA:ETHENO-NAD'>ENA</scene>, <scene name='pdbligand=RK3:(1S,3S,4R,5R,7R,15R,16S,17R)-5-imidazo[2,1-f]purin-3-yl-10,12-bis(oxidanyl)-10,12-bis(oxidanylidene)-2,6,9,11,13,18-hexaoxa-10$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{3,7}]octadecane-4,16,17-triol'>RK3</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=8btp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8btp OCA], [https://pdbe.org/8btp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8btp RCSB], [https://www.ebi.ac.uk/pdbsum/8btp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8btp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THSA_BACCS THSA_BACCS] NAD(+) hydrolyzing component (NADase) of the Thoeris antiviral defense system, composed of ThsA and ThsB. Activated by a signal molecule generated by endogenous ThsB (AC J8G8J6) or ThsB' (AC J8CSK2, probably 3'cADPR), by TIR1 and TIR2 from B.dafuensis or by BdTIR from B.distachyon (AC I1GTC2, probably 2'cADPR). Upon activation binds and hydrolyzes NAD(+), leading to cell death and inhibition of phage replication. Not seen to bind DNA (PubMed:32499527, PubMed:34853457, PubMed:36174646). Activation is 50-100x more sensitive to 3' cyclic ADP-D-ribose (3'cADPR) than 2'cADPR (PubMed:36174646). In another paper ThsA is not activated by any tested cADPR isomer, although it binds 3'cADPR; it was suggested the protein is already in a fully active state (PubMed:36048923). Expression of ThsA and ThsB in B.subtilis (strain BEST7003) confers resistance to phages phi29, SBSphiC, SBSphiJ and SPO1 (PubMed:29371424, PubMed:34853457). At multiplicity of infection (MOI) of 0.05 Thoeris-encoding cultures grow normally when infected with SPO1, at MOI 5 cultures collapse prematurely by 90 minutes post-infection, thus the phage are not able to complete a replication cycle. NAD(+) levels fall and ADP-D-ribose levels rise 60 minutes post-infection. Thoeris cultures eventually recover, but retain the same susceptibility to SPO1 (PubMed:34853457).<ref>PMID:29371424</ref> <ref>PMID:32499527</ref> <ref>PMID:34853457</ref> <ref>PMID:36048923</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Bacillus cereus MSX-D12]]
[[Category: Large Structures]]
[[Category: Sabonis D]]
[[Category: Sasnauskas G]]
[[Category: Tamulaitiene G]]