Conformational Plasticity of Parallel G-Quadruplex─Implications on Duplex-Quadruplex Motifs.

Area of Science:

• Molecular Biology
• Structural Biology
• Biophysics

Background:

• DNA G-quadruplexes are crucial nucleic acid structures with diverse biological roles.
• The parallel G-quadruplex topology is abundant and biologically significant.
• Understanding their conformational plasticity is key to elucidating their functions.

Purpose of the Study:

• To investigate the conformational plasticity of the parallel G-quadruplex topology.
• To identify the factors governing nucleotide flexibility within this structure.
• To explore the implications of this plasticity on biological interactions.

Main Methods:

• Structure survey of parallel G-quadruplexes.
• Solution-state Nuclear Magnetic Resonance (NMR) spectroscopy.
• Molecular dynamics (MD) simulations.

Main Results:

• Identified distinct flexibility patterns for nucleotides based on their position in tetrad planes.
• Correlated nucleotide flexibility with the conformational sampling of propeller loops.
• Observed differential dynamics between 5'- and 3'-terminal nucleotides, impacting duplex accommodation.

Conclusions:

• The conformational plasticity of parallel G-quadruplexes is finely tuned by nucleotide positioning and terminal dynamics.
• This plasticity is critical for processes like small molecule binding and intermolecular quadruplex stacking.
• The findings offer insights into how duplexes influence neighboring G-quadruplex structures.