9TGN

Cryo-EM structure of Z-DNA binding antibody Z-D11 in complex with left-handed Z-DNA

9TGN の概要

• エントリーDOI: 10.2210/pdb9tgn/pdb
• EMDBエントリー: 55905
• 分子名称: ZD11-VL, ZD11-VH, DNA (5'-D(*CP*GP*CP*GP*CP*GP*CP*GP*CP*GP*CP*G)-3'), ... (5 entities in total)
• 機能のキーワード: z-dna, monoclonal antibody, left-handed geometry, antibody avidity, dna binding protein
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 170549.58

構造登録者

Chin, D.H.R.,Luo, Y.B.,Luo, D. (登録日: 2025-12-02, 公開日: 2026-01-14)

主引用文献

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

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: 41415447
DOI: 10.64898/2025.12.12.693871

実験手法

ELECTRON MICROSCOPY (2.55 Å)