Molecular basis for substrate recognition and transport of mammalian taurine transporters
Abstract
The taurine transporter (TAUT) mediates cellular taurine uptake, playing a critical role in human health and longevity. In this study, we present cryogenic electron microscopy structures of both mouse and human TAUT in various conformational states. The taurine-bound, occluded forms of mouse and human TAUT reveal the substrate binding pocket and the ion binding sites. The amino group of taurine interacts with Glu406 at the binding site, constituting a key structural feature determining substrate preference. While both imidazole acetic acid and guanidinoethyl sulfonate (GES) inhibit TAUT by competing with taurine for the binding site, GES also functions as a substrate of TAUT. Moreover, mouse TAUT is captured in an inward-open apo conformation, where the tilted movement of transmembrane helix (TM) 1a opens the intracellular gate. Notably, TM6 exhibits two distinct conformational states: the canonical form consisting of two half-helices and a continuous straight helix. In the latter conformation, TM6 partially occupies the substrate binding site, likely promoting taurine release. Together, our findings provide critical insights into the molecular mechanisms by which TAUT recognizes and transports taurine.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (5)
Mingxing Wang
Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Ministry of Education Key Laboratory for Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China
Jin He
State Key Laboratory of Phytochemistry and Natural Medicines
Qianwen Cai
Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Ministry of Education Key Laboratory for Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China
Shen-ao Zhang
Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Ministry of Education Key Laboratory for Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China
Ji She
Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Ministry of Education Key Laboratory for Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China