PXD056020-1

PXD056020 is an original dataset announced via ProteomeXchange.

Title	A GAF domain mediates inositol pyrophosphate substrate channeling in PPIP5K phosphatases
Description	Inositol pyrophosphates are highly phosphorylated nutrient messengers. The final step of their biosynthesis is catalyzed by diphosphoinositol pentakisphosphate kinase (PPIP5K) enzymes, which are conserved among fungi, plants, and animals. PPIP5Ks contain an N-terminal kinase domain that generates the active messenger 1,5-InsP8 and a C-terminal phosphatase domain that participates in PP-InsP catabolism. The balance between kinase and phosphatase activities controls the cellular levels and signaling capacity of 1,5- InsP8. Here, we present crystal structures of the apo and substrate-bound Vip1 phosphatase domain from S. cerevisiae (ScVip1PD). ScVip1PD is a phytase-like inositol 1-pyrophosphate phosphatase with two conserved histidine phosphatase catalytic motifs. The enzyme has a strong preference for 1,5-InsP8 and is inhibited by inorganic phosphate. ScVip1PD has an α-helical insertion domain stabilized by a structural Zn2+ binding site, and a unique GAF domain that exists in an open and closed state, allowing channeling of the 1,5-InsP 8 substrate to the active site. Mutations that alter the active site, that restrict the movement of the GAF domain or that modify the charge of the substrate channel significantly inhibit the activity of the yeast enzyme in vitro, and the function of the Arabidopsis PPIP5K VIH2 in planta. Structural analyses of full-length PPIP5Ks suggest that the kinase and phosphatase are independent enzymatic modules. Taken together, our work reveals the structure, enzymatic mechanism and regulation of eukaryotic PPIP5K phosphatases
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-06_23:57:01.907.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056020
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Oscar Vadas
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-19 07:38:44	ID requested
⏵ 1	2024-10-06 23:57:02	announced

10.6019/PXD056020;

10.1101/2024.09.12.612650;

submitter keyword: Inositol pyrophosphate, Schizosaccharomyces pombe, histidine acid phosphatase, Arabidopsis thaliana. HDX-MS, phytase, Saccharomyces cerevisiae, enzyme mechanism, phosphate homeostasis, GAF domain, inositol pyrophosphate phosphatase

Oscar Vadas
contact affiliation	University of Geneva
contact email	oscar.vadas@unige.ch
lab head
Oscar Vadas
contact affiliation	University of Geneva, Faculty of Medicine
contact email	oscar.vadas@unige.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056020
     1. Label: PRIDE project
     2. Name: A GAF domain mediates inositol pyrophosphate substrate channeling in PPIP5K phosphatases