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Structures of the amphetamine-binding receptor will aid drug discovery

Structures of the amphetamine-binding receptor will aid drug discovery

High-resolution structures of TAAR1 — the receptor bound by amphetamines and molecules called trace amines — reveal detailed interactions with ligand molecules that will inform efforts to design antipsychotic drugs.
  1. Harald H. Sitte

    1. Harald H. Sitte is at the Center for Physiology and Pharmacology, Institute of Pharmacology, and at the Center for Addiction Research and Science, Medical University of Vienna, 1090 Vienna, Austria.
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Small molecules known as trace amines have been reported in biological materials for nearly 150 years1. They are present in the nervous systems of mammals at low levels — about 100 times lower than the concentrations of the structurally related 'monoamine' neurotransmitter compounds, such as dopamine and serotonin2 — and bind to proteins known as trace amine-associated receptors (TAARs). One of these receptors, TAAR1, has a potential role in a range of neuropsychiatric conditions, and is associated with diabetes, obesity and immune disorders. Writing in Nature, Xu et al.3 and Liu et al.4 present an astonishing 12 cryo-electron microscopy structures of human and mouse TAAR1 in complex with an array of ligand molecules. The findings will aid the development of therapeutics that bind to TAAR1.

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doi: https://doi.org/10.1038/d41586-023-03786-w

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Competing Interests

The author declares no competing interests.

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