Single-molecule transport kinetics of a glutamate transporter homolog shows static disorder.

Ciftci, Didar; Huysmans, Gerard H M; Wang, Xiaoyu; He, Changhao; Terry, Daniel; Zhou, Zhou; Fitzgerald, Gabriel; Blanchard, Scott C et al. · Sci Adv · 2020

basic_science · Level V

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Abstract

Kinetic properties of membrane transporters are typically poorly defined because high-resolution functional assays analogous to single-channel recordings are lacking. Here, we measure single-molecule transport kinetics of a glutamate transporter homolog from <i>Pyrococcus horikoshii</i>, Glt<sub>Ph</sub>, using fluorescently labeled periplasmic amino acid binding protein as a fluorescence resonance energy transfer-based sensor. We show that individual transporters can function at rates varying by at least two orders of magnitude that persist for multiple turnovers. A gain-of-function mutant shows increased population of the fast-acting transporters, leading to a 10-fold increase in the mean transport rate. These findings, which are broadly consistent with earlier single-molecule measurements of Glt<sub>Ph</sub> conformational dynamics, suggest that Glt<sub>Ph</sub> transport is defined by kinetically distinct populations that exhibit long-lasting "molecular memory."