Transmembrane receptors convey information about ligand occupancy across the membrane. The conformational changes responsible for signal transmission have been generally inaccessible due to the challenges associated with isolating full-length receptors to identify individual conformational states. We embed full-length receptors within membrane nanodiscs, a lipid bilayer encircled by a solubilizing belting protein, and use single-molecule Förster resonance energy transfer (FRET) to probe protein conformations. First, in the aspartate chemoreceptor from <i>E. coli </i>we find a change in the cytoplasmic helical packing and dynamics upon ligand occupancy, which may be a general mechanism in coiled-coil signaling proteins. Second, in the mammalian epidermal growth factor receptor (EGFR) in its monomeric form, we identify a ligand- and lipid-dependent conformational compaction, indicating a previously unappreciated extracellular and intracellular conformational coupling via a single transmembrane alpha-helix.

Single-molecule FRET measurements of transmembrane conformational dynamics of receptors in membrane nanodiscs

ACS Spring 2022

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