9KTX

Structure of TauT in complex with Guanidinoethyl sulfonate

Summary for 9KTX

• Entry DOI: 10.2210/pdb9ktx/pdb
• EMDB information: 62569
• Descriptor: Sodium- and chloride-dependent taurine transporter, Taurocyamine, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: taut, slc6a6, taurine transporter, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 70251.46

Authors

Yin, Y.X.,Lu, Y.S.,Ding, D. (deposition date: 2024-12-03, release date: 2025-12-03)

Primary citation

Lu, Y.,Ding, D.,Chen, H.,Jiang, P.,Luo, J.,Shan, H.,Wang, G.,Luo, J.,Yin, Y.
Structural determination of the human taurine transporter TauT reveals the mechanism of substrate and inhibitor recognition.
Cell Rep, 44:116591-116591, 2025

PubMed Abstract: Taurine, a sulfur-containing amino acid, is vital for human health because of its antioxidant, anti-inflammatory, and osmoregulatory properties. Its homeostasis is maintained by the Na/Cl-dependent taurine transporter (TauT). Here, we present five atomic structures of human TauT: apo, taurine bound, and complexes with three taurine-mimetic inhibitors, including β-alanine, γ-aminobutyric acid (GABA), and guanidinoethyl sulfonate (GES). The structures of taurine-, β-alanine-, and GABA-bound human TauT (hTauT) in complex with NaCl adopt an occluded conformation, with ligands binding in a central pocket. With KCl, GES-bound hTauT adopts an inward-facing conformation, with two GES positioned along the substrate translocation pathway in a bipartite manner: one in the deep central cavity and the other precluding structural transition to the occluded state. The radioactive taurine uptake analyses clearly demonstrate the impact of residues on taurine recognition and inhibitor selection. These structures provide insights into the overall architecture, substrate coordination, and inhibitor recognition mechanism of TauT.

PubMed: 41269860
DOI: 10.1016/j.celrep.2025.116591

Experimental method

ELECTRON MICROSCOPY (2.9 Å)