9ijz

Wild type Homo sapiens Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1)

Structural highlights

9ijz 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 2.91Å
Ligands:	6PL, PO4
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]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Phosphorus in crucial for all living organisms. In vertebrate, cellular phosphate homeostasis is partly controlled by XPR1, a poorly characterized inositol pyrophosphate-dependent phosphate exporter. Here, we report the cryo-EM structure of human XPR1, which forms a loose dimer with 10 transmembrane helices (TM) in each protomer. The structure consists of a scaffold domain (TM1, TM3-4) and a core domain (TM2, TM5-10) structurally related to ion-translocating rhodopsins. Bound phosphate is observed in a tunnel within the core domain at a narrow point that separates the tunnel into intracellular and extracellular vestibules. This site contains a cluster of basic residues that coordinate phosphate and a conserved W573 essential for export function. Loss of inositol pyrophosphate binding is accompanied by structural movements in TM9 and the W573 sidechain, closing the extracellular vestibule and blocking phosphate export. These findings provide insight into XPR1 mechanism and pave the way for further in-depth XPR1 studies.

Structural basis of phosphate export by human XPR1.,He Q, Zhang R, Tury S, Courgnaud V, Liu F, Battini JL, Li B, Chen Q Nat Commun. 2025 Jan 15;16(1):683. doi: 10.1038/s41467-025-55995-8. PMID:39814721^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Giovannini D, Touhami J, Charnet P, Sitbon M, Battini JL. Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep. 2013 Jun 27;3(6):1866-73. PMID:23791524 doi:10.1016/j.celrep.2013.05.035
↑ Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JR, Sears RL, Ramos EM, Spiteri E, Sobrido MJ, Carracedo A, Castro-Fernandez C, Cubizolle S, Fogel BL, Goizet C, Jen JC, Kirdlarp S, Lang AE, Miedzybrodzka Z, Mitarnun W, Paucar M, Paulson H, Pariente J, Richard AC, Salins NS, Simpson SA, Striano P, Svenningsson P, Tison F, Unni VK, Vanakker O, Wessels MW, Wetchaphanphesat S, Yang M, Boller F, Campion D, Hannequin D, Sitbon M, Geschwind DH, Battini JL, Coppola G. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4. PMID:25938945 doi:https://dx.doi.org/10.1038/ng.3289
↑ Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science. 2016 Apr 14. pii: aad9858. PMID:27080106 doi:https://dx.doi.org/10.1126/science.aad9858
↑ López-Sánchez U, Nicolas G, Richard AC, Maltête D, Charif M, Ayrignac X, Goizet C, Touhami J, Labesse G, Battini JL, Sitbon M. Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Sci Rep. 2019 May 1;9(1):6776. PMID:31043717 doi:10.1038/s41598-019-43255-x
↑ He Q, Zhang R, Tury S, Courgnaud V, Liu F, Battini JL, Li B, Chen Q. Structural basis of phosphate export by human XPR1. Nat Commun. 2025 Jan 15;16(1):683. PMID:39814721 doi:10.1038/s41467-025-55995-8

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OCA

[1] Giovannini D, Touhami J, Charnet P, Sitbon M, Battini JL. Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep. 2013 Jun 27;3(6):1866-73. PMID:23791524 doi:10.1016/j.celrep.2013.05.035

[2] Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JR, Sears RL, Ramos EM, Spiteri E, Sobrido MJ, Carracedo A, Castro-Fernandez C, Cubizolle S, Fogel BL, Goizet C, Jen JC, Kirdlarp S, Lang AE, Miedzybrodzka Z, Mitarnun W, Paucar M, Paulson H, Pariente J, Richard AC, Salins NS, Simpson SA, Striano P, Svenningsson P, Tison F, Unni VK, Vanakker O, Wessels MW, Wetchaphanphesat S, Yang M, Boller F, Campion D, Hannequin D, Sitbon M, Geschwind DH, Battini JL, Coppola G. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4. PMID:25938945 doi:https://dx.doi.org/10.1038/ng.3289

[3] Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science. 2016 Apr 14. pii: aad9858. PMID:27080106 doi:https://dx.doi.org/10.1126/science.aad9858

[4] López-Sánchez U, Nicolas G, Richard AC, Maltête D, Charif M, Ayrignac X, Goizet C, Touhami J, Labesse G, Battini JL, Sitbon M. Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Sci Rep. 2019 May 1;9(1):6776. PMID:31043717 doi:10.1038/s41598-019-43255-x

[5] He Q, Zhang R, Tury S, Courgnaud V, Liu F, Battini JL, Li B, Chen Q. Structural basis of phosphate export by human XPR1. Nat Commun. 2025 Jan 15;16(1):683. PMID:39814721 doi:10.1038/s41467-025-55995-8

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9ijz

Wild type Homo sapiens Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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