Summary information and primary citation
- PDB-id
-
9tgo;
DSSR-derived features in text and
JSON formats
- Class
- DNA binding protein
- Method
- cryo-EM (2.8 Å)
- Summary
- cryo-EM structure of z22 mab in complex with
left-handed z-DNA (dimer of trimer)
- Reference
-
Chin D, Luo Y, Lau Y, Dutta N, He Z, Yin C, Williams RM,
Balachandran S, Vicens Q, Droge P, Luo D (2025):
"Cryo-EM
structures of anti Z-DNA antibodies in complex with
antigen reveal distinct recognition modes of a
left-handed geometry." Biorxiv. doi:
10.64898/2025.12.12.693871.
- 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 <i>in situ</i> , 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)
<sub>6</sub> 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.
