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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
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Distance measurements between paramagnetic ligands bound to parallel stranded guanine quadruplexes.
1Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. matthew.donohue@nist.gov and Maryland NanoCenter, University of Maryland, College Park, MD 20742, USA.
Physical Chemistry Chemical Physics : PCCP
|May 25, 2016
Summary
Cationic porphyrins bind to guanine quadruplexes, with binding stoichiometry of 2:1. Ligand end-stacking distance decreases as quadruplex length increases, indicating structural changes in DNA secondary structure.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Deoxyribonucleic acid (DNA) can form non-canonical structures beyond the double helix.
- Guanine quadruplexes are one such structure, with potential roles in cellular processes.
- Cationic porphyrins are known to interact with guanine quadruplexes.
Purpose of the Study:
- To investigate the structural effects of cationic porphyrin binding on guanine quadruplexes with varying numbers of guanine quartets.
- To elucidate the binding stoichiometry and distances between ligands.
- To understand how ligand binding influences the secondary structure of longer guanine quadruplexes.
Main Methods:
- Utilized Double Electron-Electron Resonance (DEER) spectroscopy at X-band (9.5 GHz).
- Employed broadband, shaped inversion pulses for precise distance measurements.
- Studied model parallel-stranded guanine quadruplexes with increasing guanine quartet numbers.
Main Results:
- A 2:1 binding stoichiometry between porphyrins and each quadruplex was determined.
- Measured copper-copper distances showed a linear relationship with the number of guanines.
- Ligand end-stacking distance unexpectedly decreased as quadruplex length increased.
Conclusions:
- Cationic porphyrin binding to guanine quadruplexes is stoichiometric and distance-dependent.
- Increased quadruplex length induces conformational changes in secondary structure upon ligand binding.
- Further research is needed to fully understand these structural dynamics.
