The Deep Sea Osmolyte Trimethylamine N-Oxide and Macromolecular Crowders Rescue the Antiparallel Conformation of the Human Telomeric G-Quadruplex from Urea and Pressure Stress

Abstract

Organismsare thriving in the deepsea at pres-suresup to the 1kbar level,whichimposessevere stresson the conformationaldynamics and stabilityof theirbio-molecules.The impactofosmolytesand macromolecularcrowders, mimickingintracellular conditions,on the effectof pressure on the conformationaldynamics of ahumantelomeric G-quadruplex (G4)DNAis exploredin this studyemployingsingle-moleculeFçrsterresonanceenergytransfer(FRET)experiments.Inneat buffer,pressurizationfavorsthe parallel/hybridstateof the G4-DNAoverthe an-tiparallel conformationat 400 bar,finallyleadingtoun-foldingbeyond1000 bar.High-pressure NMRdatasupportthesefindings.The foldedtopological conformershavedifferentsolvent accessible surfaceareasandcavityvol-umes,leadingto differentvolumetricpropertiesandhencepressure stabilities.Thedeep-seaosmolytetri-methylamineN-oxide(TMAO)and macromolecular crowd-ing agentsare ableto effectively rescuethe G4-DNAfromunfolding in the wholepressure rangeencounteredonEart