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Updated: May 21, 2025

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel
Hongjiang Wu1, Liang Sun2, Tong Huo1
1Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Abstract:
Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality. Proper phosphate levels are managed through Pi import and export; and the processes governing Pi export remain the least understood. Xenotropic and Polytropic retrovirus Receptor 1 (XPR1) has been identified as the only known Pi export protein in mammals. In this study, we introduce the cryogenic electron microscopy structure of human XPR1 (hXPR1), unveiling a structural arrangement distinct from that of any known ion transporter. Our structural results suggest that hXPR1 may operate as an ion channel, a hypothesis supported by patch clamp recordings revealing hXPR1's voltage- and Pi-dependent activity and large unitary conductance. Further analyses, including the structure of hXPR1 in presence of Pi, and mutagenesis studies at one of the putative Pi binding sites, lead us to propose a plausible ion permeation pathway. Together, our results provide novel perspectives on the Pi transport mechanism of XPR1.
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