Conformational Plasticity of Parallel G-QuadruplexRImplications on Duplex-Quadruplex Motifs

DNA G-quadruplexes are essentialmotifs in molecular biology performinga wide range of functions enabled by their unique and diverse structures.In this study, we focus on the conformational plasticity of the mostabundant and biologically relevant parallel G-quadruplex topology.A multipronged approach of structure survey, solution-state NMR spectroscopy,and molecular dynamics simulations unravels subtle yet essential featuresof the parallel G-quadruplex topology. Stark differences in flexibilityare observed for the nucleotides depending upon their positioningin the tetrad planes that are intricately correlated with the conformationalsampling of the propeller loop. Importantly, the terminal nucleotidesin the 5 & PRIME;-end versus the 3 & PRIME;-end of the parallel quadruplexdisplay differential dynamics that manifests their ability to accommodatea duplex on either end of the G-quadruplex. The conformational plasticitycharacterized in this study provides essential cues toward biomolecularprocesses such as small molecular binding, intermolecular quadruplexstacking, and implications on how a duplex influences the structureof a neighboring quadruplex.