October 23, 2014

New view of transporter dynamics

New insights to the workings of a protein that moves neurotransmitters across the nerve cell membrane could aid the design of more effective antidepressants.

Transporters are proteins that use the energy stored in ion gradients to move molecules across membranes. Because of their importance in regulating the supply of essential signaling molecules such as neurotransmitters, transporters are important drug targets.

To improve drug treatment of conditions such as depression, scientists need to know not only the three-dimensional structure of transporters, but their “fourth” dimension – how their shape and function change over time.

Hassane Mchaourab, Ph.D., is a national leader in the study of protein “dynamics.” Using an electron paramagnetic spectroscopy method called double electron-electron resonance (DEER), his research team analyzed a member of a family of sodium ion-coupled transporters that in humans is involved in neurotransmitter transport.

In the Oct. 14 Proceedings of the National Academy of Sciences, they identified two distinct coupling mechanisms for substrate binding and release that were not predicted by structure alone. The finding may aid, for example, the design of more specific and effective antidepressants, the researchers said.

The research came out of Vanderbilt’s participation in the Membrane Protein Structural Dynamics Consortium, supported in part by National Institutes of Health grant GM087519.

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