9GXH

Nanobody bound to TBA G-quadruplex

Summary for 9GXH

• Entry DOI: 10.2210/pdb9gxh/pdb
• Related: 9GV4
• Descriptor: Nanobody, Thrombin-binding aptamer (TBA), POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: g-quadruplex, dna, thrombin, nanobody, thrombin-binding aptamer, tba, immune system
• Biological source: Lama glama; More
• Total number of polymer chains: 4
• Total formula weight: 36515.27

Authors

Hadzi, S.,Pevec, M. (deposition date: 2024-09-30, release date: 2025-06-11)

Primary citation

Pevec, M.,Medved, T.,Kovacic, M.,Zerjav, N.,Imperl, J.,Plavec, J.,Lah, J.,Loris, R.,Hadzi, S.
Structural basis of G-quadruplex recognition by a camelid antibody fragment.
Nucleic Acids Res., 53:-, 2025

PubMed 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.

PubMed: 40433978
DOI: 10.1093/nar/gkaf453

Experimental method

X-RAY DIFFRACTION (1.9 Å)