A small signaling domain controls PPIP5K phosphatase activity in phosphate homeostasis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 19, 2025

Abstract Inositol pyrophosphates (PP-InsPs) are eukaryotic nutrient messengers. The N-terminal kinase domain of diphosphoinositol pentakisphosphate (PPIP5K) generates the messenger 1,5-InsP 8 , C-terminal phosphatase catalyzes PP-InsP breakdown. balance between and activities regulates levels. Here, we present crystal structures apo substrate-bound PPIP5K from S. cerevisiae (ScVip1 PD ). ScVip1 is a phytase-like inositol 1-pyrophosphate histidine with two conserved catalytic motifs. enzyme has strong preference for inhibited by inorganic phosphate. It contains an α-helical insertion stabilized structural Zn 2+ binding site, unique GAF that channels substrate to active site. Mutations alter restrict movement domain, or change channel’s charge inhibit activity in vitro, Arabidopsis VIH2 planta . Our work reveals structure, enzymatic mechanism regulation phosphatases.

Язык: Английский

Tandem inactivation of inositol pyrophosphatases Asp1, Siw14, and Aps1 illuminates functional redundancies in inositol pyrophosphate catabolism in fission yeast

mBio, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

ABSTRACT Inositol pyrophosphates 5-IP 7 , 1-IP and 1,5-IP 8 are eukaryal signaling molecules that influence cell physiology, especially phosphate homeostasis. In fission yeast, impact gene expression by acting as agonists of RNA 3'-processing transcription termination. is synthesized position-specific kinases Kcs1 Asp1 convert IP 6 to respectively. pyrophosphatase enzymes (a histidine acid phosphatase), Siw14 cysteinyl Aps1 Nudix hydrolase) agents inositol pyrophosphate catabolism in yeast. Whereas Asp1, Siw14, individually inessential, double mutants asp1-H397A aps1 ∆ siw14 display severe growth defects caused overzealous 3'-processing/termination. By applying CE-ESI-MS profile the content yeast which toxicity genetically suppressed, we elucidated functional redundancies pyrophosphatases. exclusively cleaves 1-β-phosphate, Aps1, prefers cleave play essential overlapping roles guarding against accumulation toxic levels . together catabolize inositol-5-pyrophosphates, their simultaneous inactivation results overaccumulation Cells lacking all three pyrophosphatases amass high with concomitant depletion A genetic screen identified missense mutations catalytic domain kinase suppressed inositol-1-pyrophosphate toxicosis. The also implicated factor Swd22, sensor Spx1, nuclear poly(A)-binding protein Nab2 mediators toxicity. IMPORTANCE key effectors cellular They add a β-phosphate 5- or 1-phosphate groups catabolized classes hydrolyze β-phosphates pyrophosphatases—Asp1 (histidine (cysteinyl (Nudix hydrolase)—are inessential for growth, Asp1/Aps1 Aps1/Siw14 Asp1/Siw14/Aps1 triple elicit lethal defects. profiling this reveal Their synergies manifested excess upon dual an cells. absence pyrophosphatases, cells accrue while declines.

Язык: Английский

A fusion protein of polyphosphate kinase 1 (PPK1) and a Nudix hydrolase is involved in inorganic polyphosphate accumulation in the unicellular red alga Cyanidioschyzon merolae

Plant Molecular Biology, Год журнала: 2024, Номер 115(1)

Опубликована: Дек. 19, 2024

Язык: Английский