View source for 8qbm


==Retron-Eco1 filament with ADP-ribosylated Effector (full map with 2 segments)==
<StructureSection load='8qbm' size='340' side='right'caption='[[8qbm]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qbm]] is a 29 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QBM 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]] 3.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8qbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qbm OCA], [https://pdbe.org/8qbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qbm RCSB], [https://www.ebi.ac.uk/pdbsum/8qbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qbm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RT86_ECOLX RT86_ECOLX] Reverse transcriptase (RT) component of antiviral defense system retron Ec86, composed of a non-coding RNA (ncRNA), a ribosyltransferase/DNA-binding protein and this RT. Expression of the 3-gene retron confers protection against bacteriophage T5. At multiplicity of infection (MOI) of 0.02 cultures grow normally when infected with T5 without collapsing, at MOI 2 cultures enter growth stasis (PubMed:33157039). Responsible for synthesis of msDNA (a branched molecule with RNA linked by a 2',5'-phosphodiester bond to ssDNA). The retron transcript serves as primer (from a conserved internal G residue) and template for the reaction, and codes for the RT (PubMed:10531319, PubMed:2466573). Recognizes only its cognate RNA as a primer template (PubMed:10531319). Overexpression of the ncRNA and RT (without the ribosyltransferase), which leads to increased levels of msDNA, is mutagenic in vivo (PubMed:7885227). This may be due to a mismatch in the msDNA stem which binds and sequesters MutS and/or MutL (Probable).<ref>PMID:10531319</ref> <ref>PMID:2466573</ref> <ref>PMID:33157039</ref> <ref>PMID:7885227</ref> <ref>PMID:7885227</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD(+) during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD(+) hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector's toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr's pivotal role in immunity.

Retron-Eco1 assembles NAD(+)-hydrolyzing filaments that provide immunity against bacteriophages.,Carabias A, Camara-Wilpert S, Mestre MR, Lopez-Mendez B, Hendriks IA, Zhao R, Pape T, Fuglsang A, Luk SH, Nielsen ML, Pinilla-Redondo R, Montoya G Mol Cell. 2024 May 18:S1097-2765(24)00394-0. doi: 10.1016/j.molcel.2024.05.001. PMID:38788717<ref>PMID:38788717</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qbm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Carabias del Rey A]]
[[Category: Montoya G]]