8yf4

Cryo EM structure of human phosphate channel XPR1 at open and inward-facing state

spinqualitylabelsall models 8yf4, resolution 3.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8yf4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.41Å Ligands: Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease S53A1_HUMAN Bilateral striopallidodentate calcinosis. The disease is caused by variants affecting the gene represented in this entry. Function S53A1_HUMAN Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (By similarity) (PubMed:23791524, PubMed:25938945, PubMed:31043717). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106).[UniProtKB:Q9Z0U0] Publication Abstract from PubMed 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. Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.,Lu Y, Yue CX, Zhang L, Yao D, Xia Y, Zhang Q, Zhang X, Li S, Shen Y, Cao M, Guo CR, Qin A, Zhao J, Zhou L, Yu Y, Cao Y Science. 2024 Sep 26:eadp3252. doi: 10.1126/science.adp3252. PMID:39325866 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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