9grh
Crystal structure of the C-terminal phosphatase domain from Saccharomyces cerevisiae Vip1 (apo)
Structural highlights
FunctionVIP1_YEAST Bifunctional inositol kinase that acts in concert with the IP6K kinases to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17412958). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (By similarity). Required for maintaining cellular integrity, normal growth and interactions with the ARP complex (PubMed:10388810). Acts as a regulator of the PHO80-PHO85 cyclin/cyclin-dependent kinase (CDK) complex, thereby regulating signaling of phosphate availability (PubMed:17412959). Required for the function of the cortical actin cytoskeleton, possibly by participating in correct F-actin localization and ensuring polarized growth (PubMed:10388810). Regulates polarized growth and modulates interphase microtubule cytoskeleton. Regulates microtubule dynamics without the requirement of microtubule plus-end tracking protein Mal3. Required for growth zone selection (By similarity).[UniProtKB:O74429][UniProtKB:Q6PFW1][1] [2] [3] Publication Abstract from PubMedInositol pyrophosphates (PP-InsPs) are eukaryotic nutrient messengers. The N-terminal kinase domain of diphosphoinositol pentakisphosphate kinase (PPIP5K) generates the messenger 1,5-InsP(8), the C-terminal phosphatase domain catalyzes PP-InsP breakdown. The balance between kinase and phosphatase activities regulates 1,5-InsP(8) levels. Here, we present crystal structures of the apo and substrate-bound PPIP5K phosphatase domain from S. cerevisiae (ScVip1(PD)). ScVip1(PD) is a phytase-like inositol 1-pyrophosphate histidine phosphatase with two conserved catalytic motifs. The enzyme has a strong preference for 1,5-InsP(8) and is inhibited by inorganic phosphate. It contains an alpha-helical insertion domain stabilized by a structural Zn(2+) binding site, and a unique GAF domain that channels the substrate to the active site. Mutations that alter the active site, restrict the movement of the GAF domain, or change the substrate channel's charge inhibit the enzyme activity in vitro, and Arabidopsis VIH2 in planta. Our work reveals the structure, enzymatic mechanism and regulation of eukaryotic PPIP5K phosphatases. A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis.,Raia P, Lee K, Bartsch SM, Rico-Resendiz F, Portugal-Calisto D, Vadas O, Panse VG, Fiedler D, Hothorn M Nat Commun. 2025 Feb 19;16(1):1753. doi: 10.1038/s41467-025-56937-0. PMID:39966396[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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