Bile Acids as Modulators of α-Synuclein Aggregation: Implications for Parkinson's Therapy.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein into toxic amyloid fibrils. Recent research suggests that bile acids altered in PD may influence their aggregation. This study investigates the effects of lithocholic acid (LCA) and deoxycholic acid (DCA) on α-synuclein aggregation and toxicity.

Substrate-induced phase transition within liquid condensates reverses the catalytic activity of nanoparticles.

Liquid-liquid phase separation is reported to enhance the catalytic reaction rates severalfold. Herein, we explored the interactions between a catalyst and a range of substrate concentrations to understand the impact on the droplet phase and catalytic reaction kinetics. We observed that the substrate above a critical concentration induces phase transitions within liquid condensates and restricts the free movement of both the substrate and products, resulting in an overall reduction of the reaction rate, an observation not reported earlier.

Doxorubicin catalyses self-assembly of p53 by phase separation.

Liquid-liquid phase separation plays a crucial role in cellular physiology, as it leads to the formation of membrane-less organelles in response to various internal stimuli, contributing to various cellular functions. However, the influence of exogenous stimuli on this process in the context of disease intervention remains unexplored. In this current investigation, we explore the impact of doxorubicin on the abnormal self-assembly of p53 using a combination of biophysical and imaging techniques.

A single shell protein plays a major role in choline transport across the shell of the choline utilization microcompartment of 536.

Bacterial microcompartments (MCPs) are widespread protein-based organelles that play important roles in the global carbon cycle and in the physiology of diverse bacteria, including a number of pathogens. MCPs consist of metabolic enzymes encapsulated within a protein shell. The main roles of MCPs are to concentrate enzymes together with their substrates (to increase reaction rates) and to sequester harmful metabolic intermediates.

Innate and engineered attributes of bacterial microcompartments for applications in bio-materials science.

Bacterial microcompartments (BMCs) are sophisticated all-protein bionanoreactors widely spread in bacterial phyla. BMCs facilitate diverse metabolic reactions, which assist bacterial survivability in normal (by fixing carbon dioxide) and energy dearth conditions. The past seven decades have uncovered numerous intrinsic features of BMCs, which have attracted researchers to tailor them for customised applications, including synthetic nanoreactors, scaffold nano-materials for catalysis or electron conduction, and delivery vehicles for drug molecules or RNA/DNA.

Self-assembly of shell protein and native enzyme in a crowded environment leads to catalytically active phase condensates.

The self-assembly of bacterial microcompartments is the result of several genetic, biochemical, and physical stimuli orchestrating inside the bacterial cell. In this work, we use 1,2-propanediol utilization microcompartments as a paradigm to identify the factors that physically drive the self-assembly of MCP proteins in vitro using its major shell protein and major encapsulated enzyme. We find that a major shell protein PduBB' tends to self-assemble under macromolecular crowded environment and suitable ionic strength.

Disordered regions endow structural flexibility to shell proteins and function towards shell-enzyme interactions in 1,2-propanediol utilization microcompartment.

Intrinsically disordered regions in proteins have been functionally linked to the protein-protein interactions and genesis of several membraneless organelles. Depending on their residual makeup, hydrophobicity or charge distribution they may remain in extended form or may assume certain conformations upon biding to a partner protein or peptide. The present work investigates the distribution and potential roles of disordered regions in the integral proteins of 1,2-propanediol utilization microcompartments.

Barrier-free liquid condensates of nanocatalysts as effective concentrators of catalysis.

Traditional methods of molecular confinement have physicochemical barriers that restrict the free passage of substrates/products. Here, we explored liquid-liquid phase separation as a method to restrain protein-metal nanocomposites within barrier-free condensates. Confinement within liquid droplets was independent of the protein's native conformation and amplified the catalytic efficiency of metal nanocatalysts by one order of magnitude.

Light-controlled shape-changing azomacrocycles exhibiting reversible modulation of pyrene fluorescence emission.

We report the design, synthesis, and study of light-induced shape-changing azomacrocycles. These systems have been incorporated with azobenzene photoswitches using alkoxy tethers and triazole units to afford flexibility and binding. We envision that such azomacrocycles are capable of reversibly binding with the guest molecule.

A Major Shell Protein of 1,2-Propanediol Utilization Microcompartment Conserves the Activity of Its Signature Enzyme at Higher Temperatures.

A classic example of an all-protein natural nano-bioreactor, the bacterial microcompartment is a prokaryotic organelle that confines enzymes in a small volume enveloped by an outer protein shell. These protein compartments metabolize specific organic molecules, allowing bacteria to survive in restricted nutrient environments. In this work, 1,2-propanediol utilization microcompartment (PduMCP) was used as a model to study the effect of molecular confinement on the stability and catalytic activity of native enzymes in the microcompartment.

Doxorubicin induced aggregation of α-synuclein: Insights into the mechanism of drug induced Parkinsonism.

The aggregation of α-synuclein is a prominent feature of Parkinson's disease. It is induced by factors such as genetic mutations and presence of metal salts leading to Parkinson's like symptoms. Existing case studies show that patients undergoing cancer chemotherapeutics are also prone to developing Parkinson's like symptoms.

Varying protein architectures in 3-dimensions for scaffolding and modulating properties of catalytic gold nanoparticles.

Fabrication and development of nanoscale materials with tunable structural and functional properties require a dynamic arrangement of nanoparticles on architectural templates. The function of nanoparticles not only depends on the property of the nanoparticles but also on their spatial orientations. Proteins with self-assembling properties which can be genetically engineered to varying architectural designs for scaffolds can be used to develop different orientations of nanoparticles in three dimensions.

Biophysical approaches to understand and re-purpose bacterial microcompartments.

Bacterial microcompartments represent a modular class of prokaryotic organelles associated with metabolic processes. They harbor a congregation of enzymes that work in cascade within a small, confined volume. These sophisticated nano-engineered crafts of nature offer a tempting paradigm for the fabrication of biosynthetic nanoreactors.

Factors deciding the assembly and thermostability of the DmrB cage.

Dihydromethanopterin reductase (DmrB), is a naturally occurring cage protein found in various archaeal and a few bacterial species. It exists as 24mer with cubic geometry where 8 trimeric subunits are present at the corners of each cube. Each trimer is made up of three monomeric units and six FMN, where two molecules of FMN are present at the interface of each monomer.

Protein morphology drives the structure and catalytic activity of bio-inorganic hybrids.

Bio-hybrid materials have received a lot of attention in view of their bio-mimicking nature. One such biomimetic material with catalytic activity are the protein derived floral nanohybrid. Copper phosphate coordinated flakes can be curated to distinct floral morphology using proteins.

Probe into a multi-protein prokaryotic organelle using thermal scanning assay reveals distinct properties of the core and the shell.

Background: Bacterial microcompartments represent the only reported category of prokaryotic organelles that are capable of functioning as independent bioreactors. In this organelle, a biochemical pathway with all the enzyme machinery is encapsulated within an all protein shell. The shell proteins and the enzymes have distinct structural features.

Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties.

Mutations in p53 protein, especially in the DNA-binding domain, is one of the major hallmarks of cancer. The R273 position is a DNA-contact position and has several oncogenic variants. Surprisingly, cancer patients carrying different mutant variants of R273 in p53 have different survival rates, indicating that the DNA-contact inhibition may not be the sole reason for reduced survival with R273 variants.

Functional protein shells fabricated from the self-assembling protein sheets of prokaryotic organelles.

Fabricating protein compartments from protein units is challenging and limited by the use of external stimuli and crosslinkers. Here we explore the fabrication of all-protein compartments using self-assembled proteins of prokaryotic organelles. These proteins have intrinsic interacting domains which are ionic in nature, and spontaneously self-assemble into sheets when over-expressed.

The Wrappers of the 1,2-Propanediol Utilization Bacterial Microcompartments.

The propanediol utilization bacterial microcompartments are specialized protein-based organelles in Salmonella that facilitate the catabolism of 1,2-propanediol when available as the sole carbon source. This smart prokaryotic cell organelle compartmentalizes essential enzymes and substrates in a volume of a few attoliters compared to the femtoliter volume of a bacterial cell thereby enhancing the enzyme kinetics and properly orchestrating the downstream pathways. A shell or coat, which is composed of a few thousand protein subunits, wraps a chain of consecutively acting enzymes and serves as ducts for the diffusion of substrates, cofactors, and products into and out of the core of the microcompartment.

Cellulose-metallothionein matrix for metal binding.

In this report, we have modified bacterial cellulose to a metal binding matrix by covalently conjugating physiological metal chelators known as metallothioneins. The hydroxyl groups of the native bacterial cellulose from Gluconobacter xylinus are epoxidized, followed by the covalent conjugation with the amine groups of the proteins. For the first time, a covalent conjugation of protein with bacterial cellulose is achieved using the epoxy-amine conjugation chemistry.

Selective molecular transport through the protein shell of a bacterial microcompartment organelle.

Bacterial microcompartments are widespread prokaryotic organelles that have important and diverse roles ranging from carbon fixation to enteric pathogenesis. Current models for microcompartment function propose that their outer protein shell is selectively permeable to small molecules, but whether a protein shell can mediate selective permeability and how this occurs are unresolved questions. Here, biochemical and physiological studies of structure-guided mutants are used to show that the hexameric PduA shell protein of the 1,2-propanediol utilization (Pdu) microcompartment forms a selectively permeable pore tailored for the influx of 1,2-propanediol (the substrate of the Pdu microcompartment) while restricting the efflux of propionaldehyde, a toxic intermediate of 1,2-propanediol catabolism.

Diverse bacterial microcompartment organelles.

Bacterial microcompartments (MCPs) are sophisticated protein-based organelles used to optimize metabolic pathways. They consist of metabolic enzymes encapsulated within a protein shell, which creates an ideal environment for catalysis and facilitates the channeling of toxic/volatile intermediates to downstream enzymes. The metabolic processes that require MCPs are diverse and widely distributed and play important roles in global carbon fixation and bacterial pathogenesis.

Alanine scanning mutagenesis identifies an asparagine-arginine-lysine triad essential to assembly of the shell of the Pdu microcompartment.

Bacterial microcompartments (MCPs) are the simplest organelles known. They function to enhance metabolic pathways by confining several related enzymes inside an all-protein envelope called the shell. In this study, we investigated the factors that govern MCP assembly by performing scanning mutagenesis on the surface residues of PduA, a major shell protein of the MCP used for 1,2-propanediol degradation.

Mitochondrial genome variations among arsenic exposed individuals and potential correlation with apoptotic parameters.

Exposure to arsenic (As) causes serious health hazards. Therefore, there is a sustained effort to understand the molecular basis of the risk posed by the toxicant. It has been reported that apoptotic changes ensue on exposure to As.