Dr. Michael V. LeVine

October 4, 2017
11:00 – 11:50 am
C – 121

“Thermodynamic coupling in neurotransmitter reuptake”

Abstract:

The controlled reuptake of chemical neurotransmitters by transporter proteins known as neurotransmitter:sodium symporters (NSSs) is essential for normal physiological neurotransmission and is also the target of both drugs of abuse (such as cocaine and amphetamines) and therapeutics (such as antidepressants). In order to drive the otherwise thermodynamically unfavorable transport of their substrates against their concentration gradient, the NSS transporters utilize the energy provided by the sodium electrochemical gradient. They are able to perform this function due to allostery, the phenomenon in which two or more molecular processes are thermodynamically coupled. I will present new quantitative models of symport that illustrate the role of thermodynamic coupling in the context of what is currently known about the structure, biochemistry, and biophysics of this family of transporters. I will also demonstrate how we are using long timescale Molecular Dynamics simulations and our newly developed thermodynamic coupling function theory to determine the molecular mechanisms underlying allostery in the human dopamine transporter.