Phosphate Residues Research Articles

Cellular calcification induced by inorganic polyphosphate involves ATP depletion and opening of the mitochondrial permeability transition pore (mPTP).

Inorganic polyphosphate (polyP) is a linear polymer containing tens to hundreds of orthophosphate residues linked by high‐energy phosphoanhydride bonds. PolyP promotes osteocalcification and bone mineralization in both mouse and human osteoblastic cells. In the present study, we examined the molecular mechanism by which polyP affects mitochondrial metabolism to promote cellular calcification in MC3T3‐E1 osteoblastic cells. The cellular content of adenosine triphosphate (ATP) was diminished one day after polyP treatment, and this was accompanied by increased conversion to adenosine diphosphate. Furthermore, mitochondrial membrane potential was significantly decreased in polyP‐treated cells. These results suggest that the depletion of intracellular ATP and the decrease in mitochondrial membrane potential induced by polyP treatment may be a trigger to promote cell calcification.

PENGARUH PENAMBAHAN POLIFOSFAT DAN NATRIUM KLORIDA TERHADAP PENINGKATAN DAYA IKAT AIR UDANG PUTIH BEKU DAN EFISIENSI PROSES

White shrimp (Litopanaeus vannamei) is one of the most popular seafood commodities, therefore, it has considerable economic value. The aim of this study was to evaluate the effect of polyphosphate and sodium chloride addition in the soaking solution on the water holding capacity (WHC) of frozen white shrimp at a pilot scale (i.e. 12 kg), production cost efficiency and its sensory acceptance. Various combina-tions of salt and phosphates concentration were evaluated to obtain the most optimum condition for in-creasing the frozen shrimp WHC while the final product phosphate residue did not exceed 0.5%. The highest WHC was obtained by soaking the white shrimps in a solution containing 2.5% polyphosphate MTR 80-P and 1.0% NaCl. The phosphate residue concentration determined in the final product was about 0.27%. The final product multisample difference test (rating test) also confirmed that this combination was not detrimental to the perception of the consumers. Moreover, the use of soaking condition reduced the production cost (based on the raw material costs) by Rp. 4.580,900/2.000 kg finished products or equals to Rp. 2.290/kg finished products. Conclusively, the addition of polyphosphate and salt in soaking solution at the optimum concentration increased the WHC of the frozen white shrimps, reduced production cost without changing the product sensory acceptance.

Catalytic properties of wheat phytase that favorably degrades long-chain inorganic polyphosphate.

ObjectiveThis study was conducted to determine catalytic properties of wheat phytase with exopolyphosphatase activity toward medium-chain and long-chain inorganic polyphosphate (polyP) substrates for comparative purpose.MethodsExopolyphosphatase assay of wheat phytase toward polyP75 (medium-chain polyP with average 75 phosphate residues) and polyP1150 (long-chain polyP with average 1150 phosphate residues) was performed at pH 5.2 and pH 7.5. Its activity toward these substrates was investigated in the presence of Mg2+, Ni2+, Co2+, Mn2+, or ethylenediaminetetraacetic acid (EDTA). Michaelis constant (Km) and maximum reaction velocity (Vmax) were determined from Lineweaver-Burk plot with polyP75 or polyP1150. Monophosphate esterase activity toward p-nitrophenyl phosphate (pNPP) was assayed in the presence of polyP75 or polyP1150.ResultsWheat phytase dephosphorylated polyP75 and polyP1150 at pH 7.5 more effectively than that at pH 5.2. Its exopolyphosphatase activity toward polyP75 at pH 5.2 was 1.4-fold higher than that toward polyP1150 whereas its activity toward polyP75 at pH 7.5 was 1.4-fold lower than that toward polyP1150. Regarding enzyme kinetics, Km for polyP75 was 1.4-fold lower than that for polyP1150 while Vmax for polyP1150 was 2-fold higher than that for polyP75. The presence of Mg2+, Ni2+, Co2+, Mn2+, or EDTA (1 or 5 mM) exhibited no inhibitory effect on its activity toward polyP75. Its activity toward polyP1150 was inhibited by 1 mM of Ni2+ or Co2+ and 5 mM of Ni2+, Co2+, or Mg2+. Ni2+ inhibited its activity toward polyP1150 the most strongly among tested additives. Both polyP75 and polyP1150 inhibited the monophosphate esterase activity of wheat phytase toward pNPP in a dose-dependent manner.ConclusionWheat phytase with an unexpected exopolyphosphatase activity has potential as a therapeutic tool and a next-generational feed additive for controlling long-chain polyP-induced inappropriate inflammation from Campylobacter jejuni and Salmonella typhimurium infection in public health and animal husbandry.

A Kinetic Model of Oligonucleotide-Brush Interactions for the Rational Design of Gene Delivery Vectors.

Polymer brushes are attractive candidates for the design of gene delivery vectors as they allow the systematic study of the impact of structural (type, size, and shape of nanomaterials core) and physicochemical parameters (cationic monomer chemistry, brush thickness, and grafting density) on transfection efficiency. However, relatively little is known of their interactions of oligonucleotides. To study such interactions, we use surface plasmon resonance and developed a kinetic model of brush binding and infiltration. We identify the striking impact that brush grafting density and thickness have on oligonucleotide kinetics of infiltration, binding affinity, and maximum loading. Surprisingly, double-stranded RNA molecules are found to load at significantly higher levels compared to DNA molecules of identical sequence (apart from uracils/thymines). Furthermore, analysis of the kinetics of adsorption of these oligonucleotides indicates that the stoichiometry of binding (ratio of amine versus phosphate residues) is close to parity for the uptake of 20 bp double-stranded RNA. Finally, nanoparticles were designed to be used as gene transfection vectors and to quantify if the brush grafting density and thickness significantly impact transfection efficiencies in a small interfering RNA knockdown assay. Therefore, this study demonstrates the rational design of polymer brush-based nanoparticle vectors for efficient delivery of oligonucleotides. The model developed will allow to uncover how the refinement of the physicochemical and structural properties of polymer brushes enable the tuning of RNA binding and allow the systematic study of cationic vectors efficiency for RNA delivery.

Effect of light/dark cycle on nitrate and phosphate removal from synthetic wastewater based on BG11 medium by Scenedesmus sp.

In this study, microalgae growth in the synthetic wastewater and their ability to remove nutrients under different light levels was investigated. For this purpose, a comparative study was conducted on freshwater microalgae Scenedesmus sp. to evaluate their performance to remove nitrate and phosphate from both slaughterhouse and dairy synthetic treated wastewaters, under different light/dark cycles (12/12, 16/8 and 24/0h), in Erlenmeyer flasks. The best light/dark cycles in Erlenmeyer flasks for nitrate and phosphate removal and growth were obtained at 24/0h. Moreover, nitrate and phosphate removal under light conditions at 24/0h light/dark cycles were tested in a designed open raceway pond. The maximum nitrate removal in slaughterhouse and dairy synthetic wastewater was 78% and 99.7%, and the phosphate removal was 31% and 68%, respectively. Furthermore, the highest biomass productivity in dairy and slaughterhouse synthetic wastewater during 9days was 0.65gL-1 and 1.5gL-1, respectively. Thus, Scenedesmus sp. could be potential candidates by showing their intrinsic merit, for the reduction of nitrate and phosphate residue levels from dairy and slaughterhouse synthetic wastewaters in open raceway ponds.

Endocytosis of poly(ethylene sodium phosphate) by macrophages and the effect of polymer length on cellular uptake

Phosphorus-containing polymers are taking a growing interest as a bio-applicable material. Anionic poly(phosphodiester) is one type of phosphorus-containing polymer and has a similar backbone structure to teichoic acid (TA), which makes up the cell walls of gram-positive bacteria. In this study, we synthesized a copolymer of ethylene sodium phosphate and butynyl phosphate (P(EP⋅Na/BYP)), which mimics TA and, thus, should be taken up by macrophages by the same mechanism as bacterial cells. In-vitro studies showed that RAW 264.7 mammalian macrophages exhibited higher uptake of P(EP⋅Na/BYP) than L929 mammalian fibroblasts. Further, the uptake of P(EP⋅Na/BYP) by macrophages decreased in the presence of dextran sulfate; this implies that the scavenger receptor contributes to endocytosis of P(EP·Na/BYP). In-vitro studies on P(EP·Na/BYP) with different lengths (38, 85, and 127 phosphate residues) showed that P(EP·Na/BYP) with 127 phosphate residues led to the highest intracellular transportation and the least gene expressions of IL-6 and TNF-α. These results demonstrate that water-soluble poly(phosphodiester) can be used as a modifier to deliver medical drugs to macrophages.

A bioactive exopolysaccharide from marine bacteria Alteromonas sp. PRIM-28 and its role in cell proliferation and wound healing in vitro.

Marine bacteria secrete exopolysaccharides (EPS) with unique structural and functional properties and serve as a source of newer bioactive biopolymers. This study reports an EPS produced by a marine bacterium identified as Alteromonas sp. PRIM-28 for its bioactivities. The EPS was characterised using standard methods and tested for its bioactivities using in vitro models. EPS-A28 is an anionic heteropolysaccharide with a molecular weight of 780 kDa and exists as triple helical structure in aqueous solution. Monosaccharide composition is mannuronic acid, glucose and N-acetyl glucosamine repeating units in the ratio 1:3.67:0.93. The FT-IR spectra showed the presence of sulphate, phosphate and uronic acid residues. The thermal analysis showed partial degradation of the EPS-A28 at 190 °C and 40% of residues were stable up to 800 °C. It showed biocompatibility and induced proliferation and migration of dermal fibroblasts (HDF) and keratinocytes. EPS-A28 could increase the S-phase of cell cycle. The proliferative property of the EPS-A28 was established by the increased expression of fibroblast proliferation marker (Ki-67) also its capability of binding to cell surface. It also induced nitric oxide and arginase synthesis in macrophages. These findings suggest that EPS-A28 can be potentially used as a multifunctional bioactive polymer in wound care.

Several Polyphosphate Kinase 2 Enzymes Catalyse the Production of Adenosine 5'-Polyphosphates.

Polyphosphate kinases (PPKs) are involved in many metabolic processes; enzymes of the second family (PPK2) are responsible for nucleotide synthesis fuelled by the consumption of inorganic polyphosphate. They catalyse the phosphorylation of nucleotides with various numbers of phosphate residues, such as monophosphates or diphosphates. Hence, these enzymes are promising candidates for cofactor regeneration systems. Besides adenosine 5'-triphosphate, PPK2s also catalyse the synthesis of highly phosphorylated nucleotides in vitro, as shown here for adenosine 5'-tetraphosphate and adenosine 5'-pentaphosphate. These unusually phosphorylated adenosine 5'-polyphosphates add up to 50 % of the whole adenosine nucleotides in the assay. The two new products were chemically synthesised to serve as standards and compared with the two enzymatically produced compounds by high-performance ion chromatography and 31 P NMR analysis. This study shows that PPK2s are highly suitable for biocatalytic synthesis of different phosphorylated nucleotides.

How to Win the Battle with RNase.

Because ribose residues carry hydroxyl groups in both the 2' and 3' positions, RNA is chemically much more reactive than DNA and is easy prey to cleavage by contaminating RNases-enzymes with various specificities that share the property of hydrolyzing diester bonds linking phosphate and ribose residues. Because RNases are released from cells following lysis and are present on the skin, constant vigilance is required to prevent contamination of glassware and bench tops and the creation of aerosols carrying RNase. The problem is compounded because there is no simple method to inactivate RNases. Because of the presence of intrachain disulfide bonds, many RNases are resistant to prolonged boiling and mild denaturants and are able to refold quickly when denatured. Unlike many DNases, RNases do not require divalent cations for activity and thus cannot be easily inactivated by the inclusion of ethylenediaminetetraacetic acid (EDTA) or other metal ion chelators in buffer solutions. The best way to prevent problems with RNase is to avoid contamination in the first place.

The 5'-nucleotidase S5nA is dispensable for evasion of phagocytosis and biofilm formation in Streptococcus pyogenes.

5’-nucleotidases are widespread among all domains of life. The enzymes hydrolyze phosphate residues from nucleotides and nucleotide derivatives. In some pathobiontic bacteria, 5’-nucleotidases contribute to immune evasion by dephosphorylating adenosine mono-, di-, or tri-phosphates, thereby either decreasing the concentration of pro-inflammatory ATP or increasing the concentration of anti-inflammatory adenosine, both acting on purinergic receptors of phagocytic cells. The strict human pathogen Streptococcus pyogenes expresses a surface-associated 5’-nucleotidase (S5nA) under infection conditions that has previously been discussed as a potential virulence factor. Here we show that deletion of the S5nA gene does not significantly affect growth in human blood, evasion of phagocytosis by neutrophils, formation of biofilms and virulence in an infection model with larvae of the greater wax moth Galleria mellonella in S. pyogenes serotypes M6, M18 and M49. Hence, the surface-associated 5’-nucleotidase S5nA seems dispensable for evasion of phagocytosis and biofilm formation in S. pyogenes.

Inorganic polyphosphate protects against lipopolysaccharide-induced lethality and tissue injury through regulation of macrophage recruitment

Sepsis is an etiologically complex and often fatal inflammatory process involving a multitude of cytokine signaling pathways. Tumor necrosis factor α (TNFα) acts as a central regulator of the acute-phase inflammatory response by recruiting immune cells, including circulating monocyte/macrophages, to sites of infection or tissue damage. Inorganic polyphosphate (polyP), a linear polymer of orthophosphate residues, has been found in almost all cells and tissues, but its functions in immunity remain largely unknown. In this study, we show that pre- or post-treatment of mice with polyP150 (average chain length of 150 phosphate residues) markedly increases survival from lipopolysaccharide (LPS)-induced shock and inhibits macrophage recruitment to the liver and lungs, resulting in protection against tissue injury. In accord with these in vivo results, pretreatment of cultured peritoneal macrophages with polyP150 inhibited chemotaxis and actin polarization in response to TNFα. PolyP150 also inhibited phosphorylation of stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38, two downstream signaling molecules of the TNFα cascade, thereby preventing cyclooxygenase-2 gene expression by macrophages. These findings suggest that polyP150 inhibits recruitment of macrophages into organs by regulating the TNFα–JNK/p38 pathway, which may, in turn, protect against multi-organ dysfunction and lethality induced by LPS. Our findings identify polyP regulation as a novel therapeutic target for sepsis.

A Lateral Flow Immunochromato-graphic Strip Test for Rapid Detection of Oseltamivir Phosphate in Egg and Chicken Meat

A lateral flow immunochromatographic strip test (LFIST) based on a competitive format was developed for rapid and sensitive on-site detection of oseltamivir phosphate (OP) residues in poultry product. The sensitivity (half inhibitory concentration, IC50) of the LFIST in the detection of egg and chicken meat samples was confirmed to be 2.56 and 2.63 µg/kg, and the limit detection (LOD) value were 0.43 and 0.42 µg/kg, respectively. For intra-assay and inter-assay reproducibility, recoveries of OP spiked samples ranged between 82.8% and 91.2% with coefficients of variations (CV) less than 5.67% (intra-assay) and 6.52% (inter-assay). The performance of LFIST was comparable to high-performance liquid chromatography (HPLC) in a parallel testing of egg samples and chicken samples. LFIST takes less than 5 minutes, eliminates the dependency on professional personnel, and thus can be used as a surveillance tool for on-site detection of OP residues.

Pathogens Evolution During the Composting of the Household Waste Mixture Enriched with Phosphate Residues and Olive Oil Mill Wastewater

The composting of the household waste mixture enriched with phosphate residues and olive oil mill wastewater was assessed by monitoring the activity of micro-organisms during composting. During the composting process, the mixture exhibited a proliferation of actinomycetes during the thermophilic phase and during the maturation phase. Their quantities range from 11 × 102 UFC/g MF at the beginning of the process to 3.45 × 106 UFC/g MF at the end of the process. The Pseudomeunas aeruginosa and total fungi concentration show also an increase during composting from 0.2 × 106 UFC/g MF and 3.7 × 106 UFC/g MF at the start of composting to a maximun of 4.1 × 106 UFC/g MF, 5.1 × 106 UFC/g MF after 30 days. While other pathogenic microorganisms show a distinct decrease as fecal coliforms decrease from 8 × 106 UFC/g MF to 12 × 103 UFC/g MF; Escherichia coli (E. Coli) from 7.9 × 106 UFC/g MF to 14 × 103 UFC/g MF; Fecal streptococci (S.F) varied from 7.1 × 106 UFC/g MF to 10 × 104 UFC/g MF ; Staphylococcus aureus (Staph) decreased from 5.2 × 106 UFC/g MF to 8 × 104 UFC/g MF; Clostridial spores (SCR) reduced from 6.8 × 106 UFC/g MF to 11 × 103 UFC/g MF at the end of composting. A good relationship could be noted between actinomycetes and available phsosphore, and between total fungi and NTK. The pathogenic bacteria, Staph, SCR, CF, E. Coli, S.F., show more correlations with available organic components T.O.C, O.M., C/N, mainly present in the early phases of composting. The germination test shows that the water-soluble extracts of the initial stages of composting give low germination indices (GI) between 8.18 and 3.20%. After one month of composting, a successive increase of (GI) is observed to reach a maximum of 93.67% for compost after 150 days. These results provide an idea of the quality and maturity of this compost.

Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters.

Inorganic polyphosphate (polyP) is an often-overlooked biopolymer of phosphate residues present in living cells. PolyP is associated with many essential biological roles. Despite interest in polyP’s function, most studies have been limited to extracellular or isolated protein experiments, as polyanionic polyP does not traverse the nonpolar membrane of cells. To address this problem, we developed a robust, readily employed method for polyP delivery using guanidinium-rich oligocarbonate transporters that electrostatically complex polyPs of multiple lengths, forming discrete nanoparticles that are resistant to phosphatase degradation and that readily enter multiple cell types. Fluorescently labeled polyPs have been monitored over time for subcellular localization and release from the transporter, with control over release rates achieved by modulating the transporter identity and the charge ratio of the electrostatic complexes. This general approach to polyP delivery enables the study of intracellular polyP signaling in a variety of applications.

Importance of polyphosphate in the Leishmania life cycle.

Protozoan parasites contain negatively charged polymers of a few up to several hundreds of phosphate residues. In other organisms, these poly-phosphate (polyP) chains serve as an energy source and phosphate reservoir, and have been implicated in adaptation to stress and virulence of pathogenic organisms. In this study, we confirmed first that the polyP polymerase vacuolar transporter chaperone 4 (VTC4) is responsible for polyP synthesis in Leishmania parasites. During Leishmania in vitro culture, polyP is accumulated in logarithmic growth phase and subsequently consumed once stationary phase is reached. However, polyP is not essential since VTC4-deficient (vtc4-) Leishmania proliferated normally in culture and differentiated into infective metacyclic parasites and into intracellular and axenic amastigotes. In in vivo mouse infections, L. major VTC4 knockout showed a delay in lesion formation but ultimately gave rise to strong pathology, although we were unable to restore virulence by complementation to confirm this phenotype. Knockdown of VTC4 did not alter the course of L. guyanensis infections in mice, suggesting that polyP was not required for infection, or that very low levels of it suffice for lesion development. At higher temperatures, Leishmania promastigotes highly consumed polyP, and both knockdown or deletion of VTC4 diminished parasite survival. Thus, although polyP was not essential in the life cycle of the parasite, our data suggests a role for polyP in increasing parasite survival at higher temperatures, a situation faced by the parasite when transmitted to humans.

Dephosphorylation of caseins in milk protein concentrate alters their interactions with sodium hexametaphosphate

This study investigated the effects of dephosphorylation and sodium hexametaphosphate (SHMP) salt addition on the viscosity of milk protein concentrate (MPC) solutions. Dephosphorylation (DP) of casein was performed using bovine alkaline phosphatase. Nuclear magnetic resonance (NMR) spectra showed that dephosphorylation depleted the casein-bound phosphate region (CNP). SHMP addition (5 mM) had no impact on the 31P NMR spectra of DP-MPC; addition of 5 mM SHMP to control MPC (C-MPC) resulted in a shift in peaks associated with the CNP region, possibly caused by SHMP sequestering calcium, leading to swelling of micelles. DP-MPC exhibited a lower viscosity compared to C-MPC, with SHMP addition at 12.5 and 25 mM causing gelation of C-MPC and DP-MPC solutions. This work confirmed the role that phosphate residues have in maintaining micelle structural stability and provides new insights into controlling viscosity of MPC solutions.

Synthesis of nitrogen-doped carbon nanotubes-FePO4 composite from phosphate residue and its application as effective Fenton-like catalyst for dye degradation.

Phosphate residue is regarded as a hazardous waste, which could potentially create significant environmental and health problems if it is not properly treated and disposed of. In this study, nitrogen-doped carbon nanotubes-FePO4 (NCNTs-FePO4) composite was successfully synthesized from phosphate residue, and its application as an effective catalyst was explored. Firstly, an effective method was developed to recover FePO4 from phosphate residue, achieving an impressive FePO4 mass recovery rate of 98.14%. Then, the NCNTs-FePO4 catalyst was synthesized from the recovered FePO4 by two main reactions, including surface modification and chemical vapor deposition. Finally, the synthesized NCNTs-FePO4 was applied to photo-degrade 15 mg/L Rhodamine B (RhB) in a Fenton-like system. The results showed that 98.9% of RhB could be degraded in 60 min, closely following the pseudo-first-order kinetics model. It was found that even after six consecutive cycles, NCNTs-FePO4 still retained a high catalytic capacity (>50%). Moreover, •OH radicals participating in the RhB degradation process were evidenced using quenching experiments and electron paramagnetic resonance analysis, and a rational mechanism was proposed. It was demonstrated that the materials synthesized from hazardous phosphate residue can be used as an effective catalyst for dye removal.

Distribution Patterns of Polyphosphate Metabolism Pathway and Its Relationships With Bacterial Durability and Virulence.

Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate residues. It is reported to be present in all life forms. Experimental studies showed that polyP plays important roles in bacterial durability and virulence. Here we investigated the relationships of polyP with bacterial durability and virulence theoretically. Bacterial lifestyle, environmental persistence, virulence factors (VFs), and species evolution are all included in the analysis. The presence of seven genes involved in polyP metabolism (ppk1, ppk2, pap, surE, gppA, ppnK, and ppgK) and 2595 core VFs were verified in 944 bacterial reference proteomes for distribution patterns via HMMER. Proteome size and VFs were compared in terms of gain and loss of polyP pathway. Literature mining and phylogenetic analysis were recruited to support the study. Our analyzes revealed that the presence of polyP metabolism is positively correlated with bacterial proteome size and the number of virulence genes. A potential relationship of polyP in bacterial lifestyle and environmental durability is suggested. Evolutionary analysis shows that polyP genes are randomly lost along the phylogenetic tree. In sum, based on our theoretical analysis, we confirmed that bacteria with polyP metabolism are associated with high environmental durability and more VFs.

Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures

Inorganic polyphosphate is a ubiquitous, linear biopolymer built of up to thousands of phosphate residues that are linked by energy-rich phosphoanhydride bonds. Polyphosphate kinases of the family 2 (PPK2) use polyphosphate to catalyze the reversible phosphorylation of nucleotide phosphates and are highly relevant as targets for new pharmaceutical compounds and as biocatalysts for cofactor regeneration. PPK2s can be classified based on their preference for nucleoside mono- or diphosphates or both. The detailed mechanism of PPK2s and the molecular basis for their substrate preference is unclear, which is mainly due to the lack of high-resolution structures with substrates or substrate analogs. Here, we report the structural analysis and comparison of a class I PPK2 (ADP-phosphorylating) and a class III PPK2 (AMP- and ADP-phosphorylating), both complexed with polyphosphate and/or nucleotide substrates. Together with complementary biochemical analyses, these define the molecular basis of nucleotide specificity and are consistent with a Mg2+ catalyzed in-line phosphoryl transfer mechanism. This mechanistic insight will guide the development of PPK2 inhibitors as potential antibacterials or genetically modified PPK2s that phosphorylate alternative substrates.

Characterization of the Aggregation-Prone Ensemble of Tau in the Presence of Polyphosphates

Tau is a microtubule associated protein implicated in Alzheimer's disease through its aggregation and deposition as neurofibrillary tangles. Tau is both an intrinsically disordered protein and it aggregates very slowly in vitro making it challenging to study the mechanism of aggregation. Typically highly anionic molecular aggregation inducers, such as heparin, are used to induce aggregation in vitro, although these molecules are unlikely to have much physiological relevance. Recently, polyphosphates, linear chain of phosphate residues found in all prokaryotic and eukaryotic cells, have been proposed to act as a universal scaffold for the initiation of aggregation of amyloidogenic proteins. Polyphosphates have been shown to both increase the rate of amyloid fiber formation and to stabilize the fibers. Here, we use single molecule FRET to characterize conformational changes in tau in the presence of polyphosphates. The low concentrations (pM) of protein utilized in single molecule measurements allow for the population of aggregation-prone conformations, while inhibiting aggregation. In the presence of polyphosphates, tau undergoes domain specific conformational changes in which there is an overall expansion of the protein with a concomitant compaction of the microtubule binding region. Conservation of conformational shifts in the presence of different aggregation inducers will provide a model of the consensus conformational features that potentiate tau for aggregation in disease.