The allosteric mechanism of substrate-specific transport in SLC6 is mediated by a volumetric sensor.

ABSTRACT: Neurotransmitter:sodium symporters (NSSs) in the SLC6 family terminate neurotransmission by coupling the thermodynamically favorable transport of ions to the thermodynamically unfavorable transport of neurotransmitter back into presynaptic neurons. Results from many structural, functional, and computational studies on LeuT, a bacterial NSS homolog, have provided critical insight into the mechanism of sodium-coupled transport, but the mechanism underlying substrate-specific transport rates is still not understood. We present a combination of molecular dynamics simulations, single-molecule fluorescence resonance energy transfer (smFRET) imaging, and measurements of Na⁺ binding and substrate transport that reveals an allosteric substrate specificity mechanism. In this mechanism, re

SUBMITTER: LeVine MV 

PROVIDER: S-EPMC6689989 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature