Summary information and primary citation
- PDB-id
-
9gxh;
DSSR-derived features in text and
JSON formats
- Class
- immune system
- Method
- X-ray (1.9 Å)
- Summary
- Nanobody bound to tba g-quadruplex
- Reference
-
Pevec M, Medved T, Kovacic M, Zerjav N, Imperl J, Plavec
J, Lah J, Loris R, Hadzi S (2025): "Structural
basis of G-quadruplex recognition by a camelid antibody
fragment." Nucleic Acids Res.,
53. doi: 10.1093/nar/gkaf453.
- Abstract
- Apart from the iconic Watson-Crick duplex, DNA can fold
into different noncanonical structures, of which the most
studied are G-quadruplexes (G4s). Despite mounting
structural and biophysical evidence, their existence in
cells was controversial until their detection using
G4-specific antibodies. However, it remains unknown how
antibodies recognize G4s at the molecular level and
why G4-specific antibodies have low selectivity and are
unable to distinguish different G4 sequences. Here, we
present the crystal structure of a nanobody bound to the
archetypical G4 structure, the thrombin-binding aptamer
(TBA). The nanobody exhibits strong selectivity against
different G4 sequences and utilizes an unusual
scaffold-based paratope, with very limited involvement of
complementarity-determining region. The nanobody
effectively mimics the binding interface of thrombin, a
natural binding partner of TBA, by using isosteric
interactions at key positions. The presented structure
sheds light on the molecular basis of how antibodies,
essential G4-detection tools, recognize noncanonical G4
structures.
