Structure and dynamics underlying elementary ligand binding events in human pacemaking channels.

ABSTRACT: Although molecular recognition is crucial for cellular signaling, mechanistic studies have relied primarily on ensemble measures that average over and thereby obscure underlying steps. Single-molecule observations that resolve these steps are lacking due to diffraction-limited resolution of single fluorophores at relevant concentrations. Here, we combined zero-mode waveguides with fluorescence resonance energy transfer (FRET) to directly observe binding at individual cyclic nucleotide-binding domains (CNBDs) from human pacemaker ion channels critical for heart and brain function. Our observations resolve the dynamics of multiple distinct steps underlying cyclic nucleotide regulation: a slow initial binding step that must select a 'receptive' conformation followed by a ligand-induced isomer

SUBMITTER: Goldschen-Ohm MP 

PROVIDER: S-EPMC5115869 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature