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Bacillus anthracis Ser/Thr protein kinase PrkC is necessary for phenotypic memory and spore germination, and the loss of PrkC-dependent phosphorylation events affect the spore development. During sporulation, Bacillus sp. can store 3-Phosphoglycerate (3-PGA) that will be required at the onset of germination when ATP will be necessary. The Phosphoglycerate mutase (Pgm) catalyzes the isomerization of 2-PGA and 3-PGA and is important for spore germination as a key metabolic enzyme that maintains 3-PGA pool at later events. Therefore, regulation of Pgm is important for an efficient spore germination process and metabolic switching. While the increased expression of Pgm in B. anthracis decreases spore germination efficiency, it remains unexplored if PrkC could directly influence Pgm activity. Here, we report the phosphorylation and regulation of Pgm by PrkC and its impact on Pgm stability and catalytic activity. Mass spectrometry revealed Pgm phosphorylation on seven threonine residues. In silico mutational analysis highlighted the role of Thr459 residue towards metal and substrate binding. Altogether, we demonstrated that PrkC-mediated Pgm phosphorylation negatively regulates its activity that is essential to maintain Pgm in its apo-like isoform before germination. This study advances the role of Pgm regulation that represents an important switch for B. anthracis resumption of metabolism and spore germination. • Ser/Thr protein phosphorylation regulates glycolysis in B. anthracis. • Phosphorylation of glycolytic enzyme phosphoglycerate mutase (Pgm) is important in morphogenesis. • During the spore formation and germination, Pgm activity is regulated. • Unphosphorylated Pgm represents the active form, suggesting that phosphorylation has a negative effect on its function. • PrkC-dependent regulation of Pgm indicates the complexity of bacterial signaling and control of metabolism. [ABSTRACT FROM AUTHOR]

Selective compartmentalization of cellular contents is fundamental to the regulation of biochemistry. Although membrane-bound organelles control composition by using a semi-permeable barrier, biomolecular condensates rely on interactions among constituents to determine composition. Condensates are formed by dynamic multivalent interactions, often involving intrinsically disordered regions (IDRs) of proteins, yet whether distinct compositions can arise from these dynamic interactions is not known. Here, by comparative analysis of proteins differentially partitioned by two different condensates, we find that distinct compositions arise through specific IDR-mediated interactions. The IDRs of differentially partitioned proteins are necessary and sufficient for selective partitioning. Distinct sequence features are required for IDRs to partition, and swapping these sequence features changes the specificity of partitioning. Swapping whole IDRs retargets proteins and their biochemical activity to different condensates. Our results demonstrate that IDR-mediated interactions can target proteins to specific condensates, enabling the spatial regulation of biochemistry within the cell. [Display omitted] • IDRs of FUS and MED1 both form condensates but partition different proteins • Differentially partitioned proteins contain IDRs with distinct sequence features • Distinct sequence features are necessary and sufficient for differential partitioning • Swapping IDRs retargets proteins and their biochemical activity to new condensates De La Cruz et al. perform a comparative analysis of proteins differentially partitioned by two condensates and find that distinct compositions arise through specific IDR-mediated interactions. These results demonstrate that disorder-mediated interactions can target proteins to specific condensates, enabling the spatial regulation of biochemistry within the cell. [ABSTRACT FROM AUTHOR]

ZnO and Al doped ZnO films were produced by spray pyrolysis. The films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), UV-vis spectroscopy, and photoluminescence. Their photocatalytic activity was evaluated by the decomposition of the methyl orange dye using different light sources: ultraviolet light, artificial white light, and direct sunlight. The films were also tested under darkness for comparison. The ZnO films were able to degrade the test pollutant under UV and sunlight in more than a 60% after 180 min of irradiation and a scarce degradation was obtained using white light. However, the Al doped ZnO films presented a very high degradation rate not only under UV and sunlight (100% degradation), but also under white light (90% degradation after the same irradiation time). An unexpected high degradation was also obtained in the dark, which indicates that a nonphotonic process is taking place parallel to the photocatalytic process. This can be due to the extra electrons--provided by the aluminum atoms--that migrate to the surface and produce O2*- radicals favoring the decomposition process even in the dark. The high activity achieved by the ZnO: Al films under natural conditions can be potentially applied to water treatment processes. [ABSTRACT FROM AUTHOR]

Explores three Internet processor cache designs and their detailed architectural trade-offs using trace-driven simulations. Description of the baseline Internet processor cache architecture; Performance of the intelligent host address range cache; Application of the cache memory design.

Components of transcriptional machinery are selectively partitioned into specific condensates, often mediated by protein disorder, yet we know little about how this specificity is achieved. Here, we show that condensates composed of the intrinsically disordered region (IDR) of MED1 selectively partition RNA polymerase II together with its positive allosteric regulators while excluding negative regulators. This selective compartmentalization is sufficient to activate transcription and is required for gene activation during a cell-state transition. The IDRs of partitioned proteins are necessary and sufficient for selective compartmentalization and require alternating blocks of charged amino acids. Disrupting this charge pattern prevents partitioning, whereas adding the pattern to proteins promotes partitioning with functional consequences for gene activation. IDRs with similar patterned charge blocks show similar partitioning and function. These findings demonstrate that disorder-mediated interactions can selectively compartmentalize specific functionally related proteins from a complex mixture of biomolecules, leading to regulation of a biochemical pathway. [Display omitted] • Disorder-mediated selective partitioning regulates gene activation • Disordered regions are necessary and sufficient for selective partitioning • Charge patterning in disordered regions is required for specificity of partitioning • Disordered regions with similar patterning have similar partitioning and function Charge patterning in disordered regions of transcriptional regulators mediates selective partitioning into MED1IDR condensates for gene activation. [ABSTRACT FROM AUTHOR]

Parkinson's disease is characterized by the presence of insoluble and neurotoxic aggregates (amyloid fibrils) of an intrinsically disordered protein α-synuclein. In this study we have examined the effects of four naturally occurring polyphenols in combination with β-cyclodextrin (β-CD) on the aggregation of α-synuclein in the presence of macromolecular crowding agents. Our results reveal that even at sub-stoichiometric concentrations of the individual components, the polyphenol–β-CD combination(s) not only inhibited the aggregation of the proteins but was also effective in disaggregating preformed fibrils. Curcumin was found to be the most efficient, followed by baicalein with (−)-epigallocatechin gallate and resveratrol coming in next, the latter two exhibiting very similar effects. Our results suggest that the efficiency of curcumin results from a balanced composition of the phenolic OH groups, benzene rings and flexibility. The latter ensures proper positioning of the functional groups to maximize the underlying interactions with both the monomeric form of α-synuclein and its aggregates. The uniqueness of β-CD was reinforced by the observation that none of the other cyclodextrin variants [α-CD and HP-β-CD] used was as effective, in spite of these possessing better water solubility. Moreover, the fact that the combinations remained effective under conditions of macromolecular crowding suggests that these have the potential to be developed into viable drug compositions in the near future. MTT assays on cell viability independently confirmed this hypothesis wherein these combinations (and the polyphenols alone too) appreciably impeded the toxicity of the prefibrillar α-synuclein aggregates on the mouse neuroblastoma cell lines (N2a cells). [ABSTRACT FROM AUTHOR]