Structural basis of a microbial trimethylamine transporter.

Trimethylamine (TMA), a simple trace biogenic amine resulting from the decomposition of proteins and other macromolecules, is ubiquitous in nature. It is found in the human gut as well as in various terrestrial and marine ecosystems. While the role of TMA in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans has only recently been explored, many microbes are well known for their ability to utilize TMA as a carbon, nitrogen, and energy source. Here, we report the first structure of a TMA transporter, TmaT, originally identified from a marine bacterium. TmaT is a member of the betaine-choline-carnitine transporter family, and we show that TmaT is an Na IMPORTANCE: The volatile trimethylamine (TMA) plays an important role in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans and serves as a key nutrient source for a variety of ubiquitous marine microbes. While the TMA transporter TmaT has been identified from a marine bacterium, the structure of TmaT and the molecular mechanism involved in TMA transport remain unclear. In this study, we elucidated the high-resolution cryo-EM structures of TmaT and TmaT-TMA complexes and revealed the TMA binding and transport mechanisms by structural and biochemical analyses. The results advance our understanding of the TMA transport processes across biological membranes.