8YFD

Cryo EM structure of human phosphate channel XPR1 at open state

Summary for 8YFD

• Entry DOI: 10.2210/pdb8yfd/pdb
• EMDB information: 39220
• Descriptor: Solute carrier family 53 member 1 (1 entity in total)
• Functional Keywords: phosphate channel, membrane protein, phosphate homeostasis, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 92938.38

Authors

Lu, Y.,Yue, C.,Zhang, L.,Yao, D.,Yu, Y.,Cao, Y. (deposition date: 2024-02-24, release date: 2024-10-09, Last modification date: 2024-11-06)

Primary citation

Lu, Y.,Yue, C.X.,Zhang, L.,Yao, D.,Xia, Y.,Zhang, Q.,Zhang, X.,Li, S.,Shen, Y.,Cao, M.,Guo, C.R.,Qin, A.,Zhao, J.,Zhou, L.,Yu, Y.,Cao, Y.
Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.
Science, :eadp3252-eadp3252, 2024

PubMed Abstract: Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with XPR1 serving as the sole Pi exporter in humans. The mechanism of Pi efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures of XPR1 in multiple conformations, revealing a transmembrane pathway for Pi export and a dual-binding activation pattern by PP-IPs. A canonical binding site is located at the dimeric interface of SPX domains, and a second site, biased toward PP-IPs, is found between the transmembrane and SPX domains. By integrating structural studies with electrophysiological analyses, we characterize XPR1 as an IPs/PP-IPs-activated phosphate channel. The interplay among its TMDs, SPX domains, and IPs/PP-IPs orchestrates the conformational transition between its closed and open states.

PubMed: 39325866
DOI: 10.1126/science.adp3252

Experimental method

ELECTRON MICROSCOPY (3.57 Å)