9TGO
Cryo-EM structure of Z22 mAb in complex with left-handed Z-DNA (dimer of trimer)
Summary for 9TGO
| Entry DOI | 10.2210/pdb9tgo/pdb |
| EMDB information | 55906 |
| Descriptor | Z22-VH, Z22-VL, DNA (5'-D(P*CP*GP*CP*GP*CP*GP*CP*GP*CP*GP*CP*G)-3'), ... (5 entities in total) |
| Functional Keywords | z-dna, monoclonal antibody, antibody avidity, left-handed geometry, dna binding protein |
| Biological source | Mus musculus More |
| Total number of polymer chains | 16 |
| Total formula weight | 166767.60 |
| Authors | |
| Primary citation | Chin, D.,Luo, Y.,Lau, Y.,Dutta, N.,He, Z.,Yin, C.,Williams, R.M.,Balachandran, S.,Vicens, Q.,Droge, P.,Luo, D. Cryo-EM structures of anti Z-DNA antibodies in complex with antigen reveal distinct recognition modes of a left-handed geometry. Biorxiv, 2025 Cited by PubMed Abstract: 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 Zα 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 , 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) 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. PubMed: 41415447DOI: 10.64898/2025.12.12.693871 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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