A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter.

ABSTRACT: The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation. We have constructed Markov State Models (MSMs) from extensive molecular dynamics simulations of human DAT (hDAT) to explore the mechanism of this sodium release. Our results quantify the release process triggered by hydration of the Na2 sit

SUBMITTER: Razavi AM 

PROVIDER: S-EPMC5216462 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature