Formation Of Oligomers Research Articles

Nanoscale Insights into the Formation Reaction Mechanism of Si-Al Oligomers in Alkali-Activated Materials.

Alkali-activated materials (AAM) have garnered significant attention as environmentally friendly alternatives to cement due to their potential to mitigate greenhouse gas emissions and facilitate the effective utilization of industrial waste streams. Silicon-aluminum (Si-Al) monomers serve as the cornerstone units within the nanocomposite structure of AAMs, playing a pivotal role in the polycondensation reactions (PR) that govern their formation. Despite extensive research on the PR processes within AAM, the nanoscale reaction mechanisms remain elusive. In this study, MD simulations based on the ReaxFF were employed to delve into the structural evolution and reaction mechanisms of PR processes at the nanoscale. Analyses employing radial distribution functions, bond lengths, and bond angles demonstrated the robustness of the models developed in this investigation. The simulations revealed that when three Si-Al nanomolecular monomers, namely [SiO2(OH)2]2-, [SiO(OH)3]-, and [Al(OH)4]-, undergo pairwise PR, distinct reaction pathways emerge, leading to the formation of various Si-Al oligomers that collectively constitute the framework of the AAM gel. During the assembly of Si-Al oligomers, we aim to shed light on the crucial role played by Al monomers in driving the reaction forward and the subsequent polymerization of Si-Al oligomers. This disparity underscores Al's pivotal function in the PR mechanism, illuminating its indispensable role in governing the molecular architecture and kinetics of these complexes.

Molecular simulations for the effect bidispersity and crystallization temperature on the initial stage of structural formation of polyethylene oligomers upon instantaneous deep quench from their melts

Molecular simulations for the effect bidispersity and crystallization temperature on the initial stage of structural formation of polyethylene oligomers upon instantaneous deep quench from their melts

Real-Time Analysis of the Biomolecular Interaction between C1q and Amyloid-β Protein by Dual Polarization Interferometry.

Several different receptor candidates have been identified that bind monomeric, oligomeric, or fibrillar forms of amyloid-β (Aβ) protein, thus being involved in the clearance or cytotoxic action of Aβ. Component protein C1q, the initiator of the classical complement pathway, has been extensively reported to mediate neuroprotection or synapse loss through interactions with different effectors. Therefore, quantification of the C1q-Aβ interaction is a prerequisite for a better understanding of its implications in disease. Herein, we established a layer-by-layer interface sensing platform to precisely quantify the biomolecular interactions occurring between component C1q and amyloid-β protein 42 (Aβ42) in distinct morphological states. By leveraging the dual polarization interferometry (DPI) technique, we obtained real-time data pertaining to the mass, thickness, and density of the biomolecular layers during the binding process and calculated the binding dynamic parameters. From the in-depth analysis of the kinetic results and electrochemical verification, we determined that Aβ42 monomer (Aβ42M) exhibited a higher affinity for C1q than the Aβ42 oligomer (Aβ42O). This affinity could potentially account for the possibility that the C1q-Aβ42M interaction may be the first step to mediate the pivotal roles of C1q in Alzheimer's disease (AD). This study provides a new perspective on the interaction between C1q and Aβ42, and it offers new information on the C1q-involved signaling pathway to advance our understanding of the molecular mechanism of AD.

The p.K90N mutation in human HSPB5 highlights the critical role of lysine 90 in chaperone function and structural integrity.

The p.K90N mutation in human HSPB5 highlights the critical role of lysine 90 in chaperone function and structural integrity.

Enhanced detection of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) antibodies in various animal species using oligomeric nucleocapsid protein-based diagnostics

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a zoonotic pathogen that affects various animal species, often asymptomatically, while causing fatal disease in humans. Current serological tests are limited, which led to the development of novel diagnostic assays targeting the viral nucleoprotein (NP), a conserved and immunodominant protein across SFTSV strains. This study validated the new diagnostics using field monkey sera, employing Enzyme-Linked Immunosorbent Assay (ELISA) with infected cell lysate (ICL-ELISA) as the antigen. Immunoblotting with recombinant NP (rNP) demonstrated 94.6% specificity and 96.3% sensitivity for anti-NP antibody detection. As NP exists in both monomeric and RNA-binding oligomeric forms, rNP was expressed in both configurations and used for ELISA and rapid lateral flow assays (LFA). The oligomeric rNP exhibited superior antigenicity, achieving 97.3% specificity and 92.6% sensitivity, outperforming ICL-ELISA. Additionally, oligomer-enriched rNP was applied to develop an LFA test strip, where rNP conjugated with magnetic nanoparticles enhanced immunocomplex enrichment and clarity. The NP Ab-LFA test achieved 84.2% specificity and 100% sensitivity, successfully detecting anti-NP antibodies in rabbit, mouse, and monkey sera. These innovative diagnostic tools offer reliable methods for detecting SFTSV antibodies, facilitating disease control and mitigating the risk of human outbreaks.

Structural basis of BAX pore formation.

During apoptosis, cytosolic BAX monomers are translocated to the mitochondria to permeabilize the outer membrane. Here, we identified a dimer of BAX dimers as the basic repeating unit of its various oligomeric forms: arcs, lines, and rings. Cryo-electron microscopy structure of the BAX repeating unit at 3.2-angstrom resolution revealed the interactions within and between dimers. End-to-end stacking of the repeating units through the protruding α9 pairs yielded lines, arcs, polygons, and rings. We structurally characterized the tetragon, pentagon, hexagon, and heptagon, which comprise 16, 20, 24, and 28 BAX protomers, respectively. Missense mutations at the BAX inter-protomer interface damage pore formation and cripple its proapoptotic function. The assembly principle of the various BAX oligomers reported here provides the structural basis of membrane permeabilization by BAX.

The influence of proteolytic enzymes on the change of lysozyme properties

This research examines the enzymatic modification of lysozyme, a glycosidic hydrolase that has restricted effectiveness against Gram-negative bacteria, in order to produce bioactive peptide fractions with improved antibacterial and physicochemical characteristics. Utilizing chicken egg lysozyme, modifications were performed in controlled settings with proteolytic enzymes, mainly pepsin, and experiments with a pepsin-trypsin ratio. The modification methods sought to improve the hydrophobic nature of lysozyme’s surface, create oligomeric and peptide forms, and decrease immunogenicity. Findings showed that raising pepsin concentration enhanced the creation of peptide fractions, increasing surface hydrophobicity while reducing hydrolytic and antioxidant activities. Increased hydrophobicity and reduced enzyme activity were linked to enhanced antibacterial effectiveness, particularly against Gram-negative bacteria, a characteristic absent in natural lysozyme. Additionally, the research noted a decrease in immunoreactivity as pepsin concentrations increased, achieving the lowest antibody response in optimized formulations. This enzymatic method offers an economical way to create lysozyme derivatives that hold considerable promise for wider applications, particularly in scenarios where lower immunoreactivity and a prolonged antibacterial spectrum are needed.

DissectingHidden Liraglutide Oligomerization Pathwaysvia Direct Mass Technology, Electron-Capture Dissociation, and MolecularDynamics

Peptide therapeutics have revolutionized drug designstrategies,yet the inherent structural flexibility and conjugated moieties ofdrug molecules present challenges in discovery, rational design, andmanufacturing. Liraglutide, a GLP-1 receptor agonist conjugated withpalmitic acid at its lysine residue, exemplifies these challengesby forming oligomers, which may compromise efficacy through the progressiveformation of aggregates. Here, we incorporate native mass spectrometryplatforms, including electron-capture dissociation (ECD), direct masstechnology (DMT), and molecular dynamics (MD), to capture the earlyoligomerization process of liraglutide. Our findings reveal a restrictedC-terminal region upon oligomer formation, as indicated by the reducedrelease of z-ions in ECD analysis. Additionally,we identified the formation of higher-order oligomers (n = 25–62) by DMT, primarily stabilized by hydrophilic interactionsinvolving preformed stable oligomers (n = 12–18).Together, these integrative mass spectrometry results delineate adual-pathway oligomerization process for liraglutide, demonstratingthe power of mass spectrometry to uncover hidden pathways of self-association.This approach underscores the potential of mass spectrometry as akey tool in the rational design and optimization of peptide-basedtherapeutics.

Photochemical Synthesis of 2,6‐Linked Anthracene Oligomers without Introducing Extra Substituents

Photoconvertible precursors of 2,6‐linked anthracene oligomers (trimer, tetramer, and pentamer) are synthesized through repeated Suzuki–Miyaura cross‐coupling reactions. Upon exposure of these precursors to light at 450 nm, which corresponds to the n–π* transition of diketone moieties, yellow precipitates are formed, suggesting the conversion to the corresponding anthracene oligomers from the precursors. The disappearance of 1H nuclear magnetic resonance peaks after photoirradiation indicates the formation of anthracene oligomers with less solubility. High‐resolution (HR) mass spectrometry evidently indicates the oligomer formations, and infrared (IR) spectral analysis for thin films show the disappearance of peaks originating from the carbonyl groups, also supporting the conversion. The absorption spectra after photoirradiation indicate a red shift in the absorption peaks accompanying oligomer formations, suggesting an extension of the π‐conjugated system. The low solubility of the resulting anthracene oligomers in organic solvents highlights the effectiveness of this synthetic strategy using the photoconvertible precursor. This study provides a practical method to synthesize acene oligomers without the introduction of extra substituents.

The Role of Light-Harvesting Complex II Organization in the Efficiency of Light-Dependent Reactions in the Photosynthetic Apparatus of Pisum sativum L.

In this study, the functions of the photosynthetic machinery were evaluated using chlorophyll a fluorescence technique (PAM and JIP test) in pea plants (Pisum sativum L. cv Borec) and its LHC II oligomerization variants (mutants Costata 2/133 and Coeruleovireus 2/16). The oligomeric forms of LHCII increased in the following order: Costata 2/133 < Borec wt < Coeruleovireus 2/16. Data revealed that the mutant with higher LHCII oligomerization (Coeruleovireus 2/16) at low light intensity (LL, 150 µmol photons/m2·s) exhibited the following: (i) decreased energy dissipation and increased electron transport efficiency; (ii) higher reaction center density; (iii) increased amounts of the open reaction centers (qp) and their excitation efficiency (Φexc); and (iv) influenced the reoxidation of QA−, alleviating its interaction with plastoquinone. These effects enhanced photosynthetic performance related to PSII photochemistry (PIABS) and overall photosynthetic efficiency (PItotal). High light intensity (HL, 500 µmol photons/m2·s) caused a reduction in open reaction centers (qp), excitation efficiency (Φexc), photochemical energy conversion of PSII (ΦPSII), maximum efficiency of PSII photochemistry in light (Fv′/Fm′), and linear electron transport via PSII, with more pronounced effects observed in membranes with a lower degree of LHCII oligomerization (Costata 2/133). This study provides novel experimental evidence for the pivotal role of the LHCII structural organization in determining the efficiency of light-dependent reactions of photosynthesis.

A Study on the Temperature-Dependent Behavior of Small Heat Shock Proteins from Methanogens

Small heat shock proteins (sHsps) are ubiquitous low-molecular-weight chaperones that prevent protein aggregation under cellular stress conditions. In the absence of stress, they assemble into large oligomers. In response to stress, such as elevated temperatures, they undergo conformational changes that expose hydrophobic surfaces, allowing them to interact with denatured proteins. At heat shock temperatures in bacteria, large sHsp oligomers disassemble into smaller oligomeric forms. Methanogens are a diverse group of microorganisms, ranging from thermophilic to psychrophilic and halophilic species. Accordingly, their sHsps exhibit markedly different temperature dependencies based on their optimal growth temperatures. In this study, we characterized sHsps from both hyperthermophilic and mesophilic methanogens to investigate the mechanisms underlying their temperature-dependent behavior. Using analytical ultracentrifugation, we observed the dissociation of sHsps from a mesophilic methanogen into dimers. The dissociation equilibrium of these oligomers was found to be dependent not only on temperature but also on protein concentration. Furthermore, by generating various mutants, we identified the specific amino acid residues responsible for the temperature dependency observed. The C-terminal region containing the IXI/V motif and the α-crystallin domain were found to be the primary determinants of oligomer stability and its temperature dependence.

Regulatory Role of Serine59 in the Oligomeric Dynamics and Chaperone Function of αB-Crystallin.

We previously demonstrated that deletion of the 54FLRAPSW61 sequence, containing the key phosphorylation site Serine 59 (S59), resulted in a two-fold reduction in oligomeric mass and a ten-fold enhancement of αB-crystallin's chaperone activity. This study examined whether targeted deletion (ΔS59) or phosphomimetic substitution (S59D) of S59 could replicate these effects. Using MALS analysis, we found that the average oligomeric mass decreased from 579 kDa in the wild type (αB-WT) to 556 kDa in ΔS59 and 434 kDa in S59D. Interestingly, the S59A variant had an increased mass of 611 kDa. All variants retained their chaperone function, but their efficiencies varied significantly. Specifically, S59D formed smaller, more polydisperse complexes that effectively suppressed aggregation when interacting with rapidly aggregating substrates. In contrast, ΔS59 and S59A created stable complexes with lysozyme, reducing precipitation and aggregate size. Zeta potential measurements indicated distinct surface charge profiles among the variants, but there was no clear correlation between these charges and their chaperone efficiency. Additionally, cytotoxicity assays conducted on ARPE-19 cells under oxidative stress showed that all S59 variants exhibited comparable protective effects against cell death relative to αB-WT. These results indicate that while S59 is not essential for oligomer formation or chaperone function, it plays an important role in modulating oligomer size and interactions with different substrates. Notably, the effects of S59D were measurable but did not replicate the enhanced functionality observed with the complete deletion of the 54-61 motif, reinforcing the significance of the N-terminal region.

Oligomeric Protein Complexes Formed by Beta Amyloid Peptides and Their Molecular Associates.

The aggregation and dysregulation of β-amyloid (Aβ) peptides are critical factors in the pathogenesis of Alzheimer's disease (AD). This study investigates the use of reverse micelles (RMs) as a nanoscale environment to encapsulate Aβ peptides and explore their interactions with zinc ions (Zn2⁺) and a TDP-43 variant, both of which are important binding partners of Aβ peptides closely associated with neurodegenerative diseases. We demonstrate that RMs stabilize Aβ peptides in their oligomeric form, promoting β-sheet formation and enabling detailed structural studies using solid-state NMR. Our findings reveal that Zn2⁺ induces specific conformational changes in residues E11 and E22 of Aβ oligomers but not E3, and that the TDP-43 variant can form stable protein complex with Aβ40, that persists even after extended incubation and sonication. A systematic comparison of the site-specific 13C chemical shifts of the Aβ40 oligomers modulated by the interactions with Zn2⁺, Aβ42, and a TDP-43 variant, revealed that Aβ40 predominantly adopts a β1-loop-β2 motif. Notably, chemical state changes were mainly observed in the residues within the loop region and the charged residues of the β1 region. In contrast, the hydrophobic residues of the β-sheet regions were structurally unaltered upon protein complex formation.

A Machine-Learning-Based Investigation on the Formation and Evolution of Silicic Acid Oligomers Structurally Analogous to Zeolite Building Units.

A machine-learning (ML) based model that is capable of predicting the formation free energy of a silicic acid oligomer (OSA) with its SMILES string was developed and was used to investigate the formation and evolution of OSAs structurally analogous to zeolite secondary building units and composite building units (S/CBU-OSAs) to understand the mechanistic pathways for the integration of OSAs into zeolites. It was shown that most intermolecular condensation (IEC) and intramolecular condensation (IAC) forming the first cycle in OSAs are exergonic and are the major pathways for OSAs evolution. The exergonicity of an IAC depends strongly on the degree of condensation and distortion. The formation of an S/CBU-OSA is more exergonic than the competing formation of a non-S/CBU-OSA, and the exergonicity would be even greater if it were from a non-S/CBU-OSA. The work highlights the feasibility of using ML-based models to predict reaction thermodynamics and pinpoints the superior thermodynamic stability of S/CBU-OSAs.

Enhancing Peptide Cyclization: Unveiling the Key Roles of Coupling Reagents and Heat for Optimal Results.

Cyclic peptides offer several advantages over their linear counterparts, including enhanced structural stability due to their rigid conformation and increased resistance to enzymatic proteolysis. Additionally, their ring structure and constrained conformation reduce the entropic cost upon binding to receptors and other biological targets, leading to higher binding affinity and specificity. However, peptide macrocyclization is often synthetically challenging due to factors such as reduced entropy, oligomer formation, and C-terminal epimerization. The conventional approach for synthesizing cyclic peptides involves the direct coupling of amine and carboxyl termini in the solution phase, using protected side-chain peptides and coupling reagents. Despite this, improving the efficiency of head-to-tail cyclization remains a key challenge. In this study, the cyclization of a de novo octapeptide composed of alternating l- and d-amino acids is optimized, in which the impact of various factors on the cyclization process is examined, including coupling reagents, temperature, heating method, chaotropic agents, solvent, and concentration. This investigation has not only led to the identification of efficient cyclization conditions, but also provides a valuable framework for the cyclization of other challenging peptide sequences. The insights gained in this study contribute to the field of peptide chemistry, expanding the understanding of peptide cyclization reactions.

Differentiation of SH-SY5Y Cells into Cortical Neuron-like Cells for Tauopathy Modeling and Seeding Assays.

SH-SY5Y cells are widely used as an in vitro neuronal model, yet reliable differentiation protocols tailored for tauopathy research remain limited. Effective differentiation is essential for studying tau aggregation, propagation, and neurodegenerative mechanisms. Here, we present an optimized two-step differentiation protocol for TauP301L-expressing SH-SY5Y cells that enhances neuronal maturation and tauopathy modeling, providing a physiologically relevant system for investigating tau seeding. SH-SY5Y cells expressing TauP301L-EGFP under an inducible system were differentiated using a two-step protocol consisting of retinoic acid (RA) for 72h, followed by brain-derived neurotrophic factor (BDNF) and RA for 72h. Differentiated neurons were then exposed to exogenous P301L tau peptidefibrils to assess their susceptibility to tau seeding and aggregation. Differentiation resulted in increased neurite outgrowth, cholinergic marker expression (ChAT upregulation, TH downregulation), and upregulation of the mature 2N4R tau isoform. Western blot analysis showed increased T22 and pSer262 tauimmunoreactivity in seeded cells, consistent with tau conformational changes and pathological phosphorylation. These findings may reflect early stages of tau misfolding but do not confirm oligomer formation. Seeding also induced neurite remodeling, varicosity formation, and reduced neurite diameter-features consistent with tau-mediated pathology involving cytoskeletal changes, organelle accumulation, or axonal transport defects. This optimized differentiation protocol provides an experimentally tractable tauopathy model for investigating tau propagation and neuronal dysfunctions in a controlled human cell context. Compared to existing SH-SY5Y differentiation methods, our system provides faster neuronal maturation, controlled TauP301L induction, and enhanced tau isoform expression, making it a valuable platform for studying early tau misfolding events and therapeutic interventions in tauopathies.

Oligomerisation of pentraxin-3: Insights from cryoEM.

Oligomerisation of pentraxin-3: Insights from cryoEM.

Cryo-EM structure provides insights into the unusual heptameric assembly of rice (Oryza sativa L.) ClpB1 AAA+ ATPase.

Cryo-EM structure provides insights into the unusual heptameric assembly of rice (Oryza sativa L.) ClpB1 AAA+ ATPase.

Novel role of Silver(I) as electron shuttle for polymerization of chlorophenols by permanganate oxidation.

Novel role of Silver(I) as electron shuttle for polymerization of chlorophenols by permanganate oxidation.

Imaging oligomers of alpha-toxin (Hla) variants using high-speed AFM and neutralizing Hla hemolytic activity with their antisera.

Imaging oligomers of alpha-toxin (Hla) variants using high-speed AFM and neutralizing Hla hemolytic activity with their antisera.