View source for 9tgw


==Cryo-EM structure of Z22 antibody in complex with left-handed Z-DNA (trimer)==
<StructureSection load='9tgw' size='340' side='right'caption='[[9tgw]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9tgw]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9TGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9TGW 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]] 2.67&#8491;</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=9tgw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9tgw OCA], [https://pdbe.org/9tgw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9tgw RCSB], [https://www.ebi.ac.uk/pdbsum/9tgw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9tgw ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Double-stranded nucleic acids can undergo transitions from canonical B/A-forms to alternate left-handed Z-DNA/Z-RNA (Z-NAs). Z-NAs are implicated in processes such as neuroinflammation in Alzheimer's disease, Lupus Erythematosus, microbial biofilms, and type I interferon-mediated human pathologies. Since endogenous Z-NA sensors like the Zalpha domain can induce B-to-Z transitions, monoclonal antibodies (mAbs) Z-D11 and Z22 have been regarded as conformation-specific tools to confirm Z-NA in situ , although high-resolution structural information is missing. Here, we employed single-particle cryo-electron microscopy to solve structures of Z-D11 and Z22 bound to synthetic d(CG) (6) 12mer Z-DNA duplex. Both mAbs form filamentous trimers around the Z-DNA axis, further stabilized by Fab-Fab interactions. The mAbs achieve specificity through extensive contacts to both Z-form backbone strands and the exposed guanine/cytosine bases in the major groove. This mode of recognition is dictated by shape complementarity rather than sequence specificity, sensing the alternating syn/anti backbone torsions and the phosphate zig-zag geometry unique to Z-DNA. Our data also suggest that these mAbs are not inducing B-to-Z transitions under normal physiological conditions. Finally, comparison to other double-stranded NA-binding mAbs defines a similar structural logic adapted to different helical geometry recognition patterns, thus providing a framework for engineering highly specific nucleic acid probes.

Cryo-EM structures of anti Z-DNA antibodies in complex with antigen reveal distinct recognition modes of a left-handed geometry.,Chin D, Luo Y, Lau Y, Dutta N, He Z, Yin C, Williams RM, Balachandran S, Vicens Q, Droge P, Luo D bioRxiv [Preprint]. 2025 Dec 12:2025.12.12.693871. doi: , 10.64898/2025.12.12.693871. PMID:41415447<ref>PMID:41415447</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9tgw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chin DHR]]
[[Category: Luo D]]
[[Category: Luo YB]]