The stereochemistry of the inositol backbone provides a platform on which to generate a vast array of distinct molecular motifs that are used to convey information both in signal transduction and many other critical areas of cell biology. Diphosphoinositol phosphates, or inositol pyrophosphates, are the most recently characterized members of the inositide family. They represent a new frontier with both novel targets within the cell and novel modes of action. This includes the proposed pyrophosphorylation of a unique subset of proteins. We review recent insights into the structures of these molecules and the properties of the enzymes which regulate their concentration. These enzymes also act independently of their catalytic activity via protein-protein interactions. This unique combination of enzymes and products has an important role in diverse cellular processes including vesicle trafficking, endo- and exocytosis, apoptosis, telomere length regulation, chromatin hyperrecombination, the response to osmotic stress, and elements of nucleolar function.
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http://dx.doi.org/10.1007/s00018-009-0115-2 | DOI Listing |
Nat Commun
January 2025
Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China.
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.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Faculty of Science and Engineering, Department of Biology, Konan University, Kobe, Japan; Institute of Integrative Neurobiology, Konan University, Kobe, Japan. Electronic address:
Phosphate (Pi) homeostasis at the cellular level is crucial, requiring coordinated Pi uptake, storage, and export. However, the regulatory mechanisms, particularly those governing Pi export, remain elusive, despite their relevance to human diseases like primary familial brain calcification. While Xpr1, conserved across eukaryotes, is the only known Pi exporter, the existence of additional Pi exporting factors is evident; however, these factors have been poorly characterized.
View Article and Find Full Text PDFMetabolism
February 2025
Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:
Background And Aims: Atherosclerotic cardiovascular diseases are the leading cause of death. Apolipoprotein A-I (apoA-I) mediates cholesterol efflux to lower the risks of atherosclerosis. Elevating circulating apoA-I is an effective strategy for atheroprotection.
View Article and Find Full Text PDFPLoS Genet
November 2024
Structural Plant Biology Laboratory, Department of Plant Sciences, University of Geneva, Geneva, Switzerland.
Inositol pyrophosphates (PP-InsPs) are nutrient messengers whose cellular levels are precisely regulated. Diphosphoinositol pentakisphosphate kinases (PPIP5Ks) generate the active signaling molecule 1,5-InsP8. PPIP5Ks harbor phosphatase domains that hydrolyze PP-InsPs.
View Article and Find Full Text PDFJ Exp Bot
November 2024
Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, Telangana,India.
Phosphorus (P) is a quintessential macronutrient utilized by plants to support various metabolic processes during growth and development. Recent studies have revealed the pivotal role of inositol hexa-kis/pyrophosphate (InsP6-8), the derivatives of Myo-inositol (MI), in facilitating the interaction between SYG1/PHO81/XPR1 (SPX) and Phosphate starvation response (PHR) proteins. Myo-inositol phosphate synthase (MIPS) catalyzes the first committed step in MI biosynthesis.
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