8TYV
Crystal structure of the SPX domain of XPR1 in complex with IP8
Summary for 8TYV
| Entry DOI | 10.2210/pdb8tyv/pdb |
| Descriptor | Solute carrier family 53 member 1, (1R,3S,4R,5S,6R)-2,4,5,6-tetrakis(phosphonooxy)cyclohexane-1,3-diyl bis[trihydrogen (diphosphate)] (3 entities in total) |
| Functional Keywords | transferase, inositol diphosphoinositol pentakisphosphate kinase, analog methylenebisphosphonate, ppip5k atp-grasp, pyrophosphate diphosphate |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 42797.26 |
| Authors | Wang, H.,Shears, S.B. (deposition date: 2023-08-25, release date: 2024-06-12, Last modification date: 2024-12-25) |
| Primary citation | Li, X.,Kirkpatrick, R.B.,Wang, X.,Tucker, C.J.,Shukla, A.,Jessen, H.J.,Wang, H.,Shears, S.B.,Gu, C. Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. Cell Rep, 43:114316-114316, 2024 Cited by PubMed Abstract: Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake. This direct, regulatory interplay arises from XPR1 being a binding partner for the Pi uptake transporter PiT1, involving a predicted transmembrane helix/extramembrane loop in XPR1, and its hitherto unknown localization in a subset of intracellular LAMP1-positive puncta (named "XLPVs"). A pharmacological mimic of Pi homeostatic challenge is sensed by the inositol pyrophosphate IP, which functionalizes XPR1 to respond in a temporally hierarchal manner, initially adjusting the rate of Pi efflux, followed subsequently by independent modulation of PiT1 turnover to reset the rate of Pi uptake. These observations generate a unifying model of mammalian cellular Pi homeostasis, expanding opportunities for therapeutic intervention. PubMed: 38833370DOI: 10.1016/j.celrep.2024.114316 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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