Structure of the sodium-dependent phosphate transporter reveals insights into human solute carrier SLC20
Open Access
- 1 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (32), eabb4024
- https://doi.org/10.1126/sciadv.abb4024
Abstract
Inorganic phosphate (P-i) is a fundamental and essential element for nucleotide biosynthesis, energy supply, and cellular signaling in living organisms. Human phosphate transporter (hPiT) dysfunction causes numerous diseases, but the molecular mechanism underlying transporters remains elusive. We report the structure of the sodium-dependent phosphate transporter from Thermotoga maritima (TmPiT) in complex with sodium and phosphate (TmPiT-Na/Pi) at 2.3-angstrom resolution. We reveal that one phosphate and two sodium ions (Pi-2Na) are located at the core of TmPiT and that the third sodium ion (Na-fore) is located near the inner membrane boundary. We propose an elevator-like mechanism for sodium and phosphate transport by TmPiT, with the TmPiT-Na/Pi complex adopting an inward occluded conformation. We found that disease-related hPiT variants carry mutations in the corresponding sodium- and phosphate-binding residues identified in TmPiT. Our three-dimensional structure of TmPiT provides a framework for understanding PiT dysfunction and for future structure-based drug design.Funding Information
- Ministry of Science and Technology, Taiwan (108-2321-B-007-002)
- Ministry of Science and Technology, Taiwan (107-2311-B-001-032-MY3)
- Ministry of Science and Technology, Taiwan (108-2811-B-007-504)
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