Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex
Yangyuoru, Philip M
Di, Antonio Marco
Angewandte Chemie International Edition (English)
MetadataShow full item record
Yangyuoru, P. M., Di, A. M., Ghimire, C., Biffi, G., Balasubramanian, S., & Mao, H. (2014). Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex. Angewandte Chemie International Edition (English), 54 910-913. https://doi.org/10.1002/anie.201408113
In investigating the binding interactions between the human telomeric RNA (TERRA) G-quadruplex (GQ) and its ligands, it was found that the small molecule carboxypyridostatin (cPDS) and the GQ-selective antibody BG4 simultaneously bind the TERRA GQ. We previously showed that the overall binding affinity of BG4 for RNA GQs is not significantly affected in the presence of cPDS. However, single-molecule mechanical unfolding experiments revealed a population (48 %) with substantially increased mechanical and thermodynamic stability. Force-jump kinetic investigations suggested competitive binding of cPDS and BG4 to the TERRA GQ. Following this, the two bound ligands slowly rearrange, thereby leading to the minor population with increased stability. Given the relevance of G-quadruplexes in the regulation of biological processes, we anticipate that the unprecedented conformational rearrangement observed in the TERRA-GQ–ligand complex may inspire new strategies for the selective stabilization of G-quadruplexes in cells.
G-quadruplexes, ligand effects, optical traps, RNA structures, single-molecule studies
H.M. acknowledges support from NSF CHE-1026532. The Balasubramanian lab is supported by programme funding from Cancer Research UK.
External DOI: https://doi.org/10.1002/anie.201408113
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247067
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
Recommended or similar items
The following licence files are associated with this item: