Researchers at St. Jude Children’s Research Hospital have uncovered the structure of VMAT2, a crucial neurotransmitter transporter, shedding light on its interaction with drugs used to treat conditions like Tourette syndrome. This pioneering study offers insights into neurotransmitter transport and advances the field of neuropharmacology.
Neurons communicate through neurotransmitters, and experts at St. Jude Children’s Research Hospital have utilized their knowledge in structural biology to reveal the structure of vesicular monoamine transporter 2 (VMAT2), an essential component of neurotransmission.
By visualizing VMAT2 in different states, researchers can now better comprehend its function and how its different conformations impact drug binding. This knowledge is crucial for the development of drugs to treat hyperactivity disorders such as Tourette syndrome.
This work was recently published in the journal Nature. Monoamines, including dopamine, serotonin, and adrenaline, play a central role in neurotransmission by influencing various brain functions. Before they can be released, these molecules must be packaged into vesicles, which are compartments in cells that store neurotransmitters.
VMAT2 is a protein that moves monoamines into these vesicles, acting like a loading crane on a cargo ship. The study, led by researchers such as Dr. Chia-Hsueh Lee, Dr. Shabareesh Pidathala, and Dr. Yaxin Dai, utilized cryo-electron microscopy to analyze the structure of VMAT2 and its interactions with serotonin and drugs used to treat certain conditions.
The study revealed that different drugs bind to specific conformations of VMAT2, providing detailed insights that can aid in developing treatments for various disorders. The research also identified amino acids that facilitate neurotransmitter transport, laying the groundwork for future studies to fully understand the mechanisms involved.
The study was supported by grants from organizations such as the National Institutes of Health and the National Natural Science Foundation of China.
Source: scitechdaily.com
