Structure-function Relationships Research Articles

Exploring the Structure–Function Relationship in Iridium–Cobalt Oxide Catalyst for Oxygen Evolution Reaction across Different Electrolyte Media

Exploring the Structure–Function Relationship in Iridium–Cobalt Oxide Catalyst for Oxygen Evolution Reaction across Different Electrolyte Media

Unravelling the Digestibility and Structure-Function Relationship of Lentil Protein Through Germination and Molecular Weight Fractionation.

This study explores for the first time the impact of a 6-day germination process on the structure (FTIR), antioxidant activity, nutritional/safety attributes (ACE-I inhibitory activity, digestibility, and cytotoxicity), and functional properties of fractions of variable molecular weight (W > 5 kDa; 3 kDa < MW < 5 kDa; and MW < 3 kDa) isolated from proteins extracted from lentils. FTIR results indicated a substantial increase in β-sheet contents during germination. The digestibility of proteins increased from day 0 (16.32-17.04%) to day 6 of germination (24.92-26.05%) with variable levels of digestibility depending on their MW. ACE-I inhibitory activity improved during germination in all fractions, reaching IC50 values of 0.95, 0.83, and 0.69 mg/mL after 6 days of germination. All antioxidant activities analyzed notably increased, particularly in low-MW fractions (MW < 3 kDa). The functional properties of low-MW fractions were also the most promising, displaying the highest water and fat binding capacities and emulsifying and foaming capacities but lower foaming and emulsifying stability compared to high-MW fractions. Cytotoxicity tests on L929 cells revealed the slight adverse effects of low-MW fractions during germination. This study provides insights into the enhanced nutritional and functional attributes of lentil proteins following germination, emphasizing their potential application in functional foods.

Teaching Pathological Physiology of Sepsis Using a High Fidelity Simulator.

A good knowledge of the theoretical foundations of medicine helps students and physicians to better recognize and treat patients with complex medical conditions, including sepsis and septic shock. The article describes the authors' experience in implementing the analysis of sepsis and septic shock using a high-fidelity simulated clinical scenario in the course of pathological physiology for preclinical medical students. The unique aspect of our approach is the integration of core physiology concepts, such as homeostasis, causality, structure-function relationships, and fundamental pathophysiology concepts (e.g., etiology, pathogenesis, cell and tissue damage, inflammation, symptoms and syndromes), in the analysis of the patient's condition on the high fidelity simulator with preclinical medical students. According to the students' feedback, the use of a high-fidelity simulator to analyze the sepsis and septic shock scenario increased their interest in the class, improved their motivation to learn the material, and helped them adapt in a safe environment to making decisions based on a large amount of data about a complex patient condition in a time-sensitive situation.

Molecular Determinants of Protein Pathogenicity at the Single-Aggregate Level.

Determining the structure-function relationships of protein aggregates is a fundamental challenge in biology. These aggregates, whether formed in vitro, within cells, or in living organisms, present significant heterogeneity in their molecular features such as size, structure, and composition, making it difficult to determine how their structure influences their functions. Interpreting how these molecular features translate into functional roles is crucial for understanding cellular homeostasis and the pathogenesis of various debilitating diseases like Alzheimer's and Parkinson's. In this study, a bottom-up approach is introduced to explore how variations in protein aggregates' size, composition, post-translational modifications and point mutations profoundly influence their biological functions. Applying this method to Alzheimer's and Parkinson's associated proteins, novel disease-relevant pathways are uncovered, demonstrating how subtle alterations in composition and morphology can shift the balance between healthy and pathological states. This findings provide deeper insights into the molecular basis of protein's functions at the single-aggregate level, enhancing the knowledge of their roles in health and disease.

Pyrrolopyrrole Cyanine J-Aggregates with Amplified Superoxide Radical Generation, GSH Depletion, and Photothermal Action for Hypoxic Cancer Phototherapy.

The elevated glutathione (GSH) level and hypoxia in tumor cells are two key obstacles to realizing the high performance of phototherapy. Herein, the electron-donating rotors are introduced to wings of electron-withdrawing pyrrolopyrrole cyanine (PPCy) to form donor-acceptor-donor structure J-aggregates for amplified superoxide radical generation, GSH depletion, and photothermal action for hypoxic cancer phototherapy to tackle this challenge. Three PPCy photosensitizers (PPCy-H, PPCy-Br, and PPCy-TPE) produce hydroxyl radicals (•OH) and superoxide radicals (O2•-) in hypoxia tumors exclusively as well as excellent photothermal performances under light irradiation. More importantly, GSH as an "electron reservoir" could effectively participate in photoredox processes, continuously consuming GSH and simultaneously generating more superoxide radicals. Notably, the structure-function relationship results reveal that PPCy-TPE nanoparticles (NPs) possess a high molar extinction coefficient (8.5 × 104 M-1 cm-1 at 778 nm) with the broadest absorption band in the near-infrared region, the most significant type I total ROS enhancement, and the highest photothermal conversion efficiency (41.3%). Furthermore, PPCy-TPE NPs have been successfully applied for in vitro and in vivo hypoxic cancer phototherapy under an 808 nm laser with outstanding specificity and biological safety. This work provides a promising single phototherapy agent against hypoxic tumors with efficient type I PDT/PTT synergistic therapy.

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain.

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left. Here, we ask whether neuroanatomical asymmetries can be observed in mice, leveraging 6 mouse neuroimaging cohorts from 5 different research groups (∼3,500 animals). We found an anterior-posterior pattern of volume asymmetry with anterior regions larger on the right and posterior regions larger on the left. This pattern appears driven by similar trends in surface area and positional asymmetries, with the results together indicating a small brain-wide twisting pattern, similar to the human cerebral petalia. Furthermore, the results show no apparent relationship to known functional asymmetries in mice, emphasizing the complexity of the structure-function relationship in brain asymmetry. Our results recapitulate and extend previous patterns of asymmetry from two published studies as well as capture well-established, bilateral male-female differences in the mouse brain as a positive control. By establishing a signature of anatomical brain asymmetry in mice, we aim to provide a foundation for future studies to probe the mechanistic underpinnings of brain asymmetry seen in humans - a feature of the brain with extremely limited understanding.

Unveiling the potential of bean proteins: Extraction methods, functional and structural properties, modification techniques, physiological benefits, and diverse food applications.

Bean proteins, known for their sustainability, versatility, and high nutritional value, represent a valuable yet underutilized resource, receiving less industrial attention compared to soy and pea proteins. This review examines the structural and molecular characteristics, functional properties, amino acid composition, nutritional value, antinutritional factors, and digestibility of bean proteins. Their applications in various food systems, including baked goods, juice and milk substitutes, meat alternatives, edible coatings, and 3D printing inks, are discussed. The physiological benefits of bean proteins, such as antidiabetic, cardioprotective, antioxidant, and neuroprotective effects, are also presented, highlighting their potential for promoting well-being. Our review emphasizes the diversity of bean proteins and highlights ultrasound as the most effective extraction method among available techniques. Beyond their physiological benefits, bean proteins significantly enhance the structural, technological, and nutritional properties of food systems. The functionality can be further improved through various modification techniques, thereby expanding their applicability in the food industry. While studies have explored the impact of bean protein structure on their nutritional and functional properties, further research is needed to investigate advanced modification techniques and the structure-function relationship. This will enhance the utilization of bean proteins in innovative and sustainable food applications.

High hydrostatic pressure promotes gene transcription via a cystathionine-β-synthase domain-containing protein in the hyperthermophilic archaeon Pyrococcus yayanosii.

Cystathionine-β-synthase (CBS) domains are ubiquitously prevalent in all kingdoms of life. Remarkably, in archaea, proteins consisting of solely CBS domains are widespread. However, the biological functions of CBS proteins in archaea are still unknown. Here, we identified a high hydrostatic pressure regulator (HhpR) that comprises four CBS domains serving as a transcriptional activator via specifically binding to the UAS (upstream activating sequence) motif situated within the promoter region of an operon in a hyperthermophilic archaeon Pyrococcus yayanosii under high hydrostatic pressure (HHP). By combining molecular dynamics simulations,in vitro and in vivo assays, we revealed the potential binding interfaces between HhpR and its specific DNA binding site. Particularly, one stem-loop region in HhpR (termed as 'Arm') was found to play a critical role in regulating the transcription activity,and the 192 position in the Arm region is an essential site in dictating the conformational changes of HhpR at HHP condition. Our work provides novel insights into the structure-function relationship of CBS-containing proteins that participate in archaeal gene regulation as general transcriptional activators.

Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition.

The structural plasticity of proteins at the molecular level is largely dictated by backbone torsion angles, which play a critical role in ligand recognition and binding. To establish the anion-induced cooperative arrangement of the main-chain (mc) torsion, herein, we analyzed a set of naturally occurring CαNN motifs as "static models" for their anion-binding competence through docking and molecular dynamics simulations and decoded its torsion angle influenced mc-driven anion recognition potential. By comparing a pool of 20 distinct sets of CαNN motif with identical sequences in their "anion bound/present, aP" and "anion free/absent, aA" versions, we could discern that there exists a positive correlation between the "difference of anion residence time (ΔRT)" and "difference among the main-chain torsion angle" of the aP and aA population. Notably, the anion interaction with CαNNs is locally energetically favorable even in a context-free non-proteinaceous environment and if the difference of the mc-torsion angles involving the Cα-1, N0, N1 residues for a population is higher between the aP and aA state, the difference among the ligand RT is also greater. At the atomistic level, the accommodation of anion is highly synergistic and cooperatively sways the interacting mc-atom torsions. By comparing the clustering of H-bonding patterns, the free energy of binding, and RT in both states, we provide evidence that to establish favorable thermodynamics and kinetics of ligand accommodation in these short structural motifs, proper reorientation of local-mc governed by torsions is a prerequisite. Our findings position the CαNN motif as a promising scaffold for peptidomimetic design and emphasize the critical role of loop region dynamics in protein structure-function relationships.

Structural analysis of a membrane-associated delta-6 fatty acid desaturase from Prorocentrum micans.

Delta-6 fatty acid desaturases, which play key roles in the biosynthesis of polyunsaturated fatty acids (PUFAs), are membrane-associated enzymes that present significant challenges for isolation and purification, complicating their structural characterization. Here we report the identification and structure-function analysis of a novel Δ6 fatty acid desaturase (PmD6) from the marine alga Prorocentrum micans with substrate preference to α-linolenic acid (18:3n-3). Structural modeling revealed a mushroom-like structure of PmD6 formed by four transmembrane α-helices as a stem and three cytoplasmic domains as a cap. Structural alignment identified several key residues positioned around the substrate tunnel and catalytic center in PmD6. Functional analysis of these residues by site-directed mutagenesis showed that Tyr226, Trp235, Phe345, and Ser349, facing the middle region of the substrate tunnel of PmD6, played critical roles in defining the structure for acceptance of substrates. Thr200, Leu391, and Met389, surrounding the end of the substrate tunnel, had roles in interaction with the methyl end of substrates. Asp255, close to a metal iron in the catalytic center, was essential for catalytic reaction by supporting the regional structure. These results have provided mechanistic insights into the structure-function relationship of membrane-bound front-end fatty acid desaturases.

Preparation, structural property, and antioxidant activities of a novel pectin polysaccharide from the flowers of Hibiscus syriacus Linn.

Oxidative stress, triggered by an imbalance between reactive oxygen species (ROS) production and cellular antioxidant defense mechanisms, is implicated in various pathological conditions. Plant-derived polysaccharides have gained significant attention as potential natural antioxidants due to their biocompatibility, biodegradability, and structural versatility. This study focuses on the purification, structural characterization, and antioxidant activities of a novel pectin polysaccharide (HFPS) isolated from the flowers of Hibiscus syriacus Linn. HFPS was purified using anion-exchange chromatography. Its chemical composition, monosaccharide profile, molecular weight distribution, and structural properties were elucidated through various analytical techniques. HFPS exhibited a predominant acidic monosaccharide composition, with galacturonic acid as the major constituent, indicating its pectin nature. The free radical scavenging activity of HFPS against ABTS·, DPPḤ, and ·OH radicals was evaluated, demonstrating a positive correlation between its antioxidant capacity and concentration. Furthermore, HFPS effectively protected HepG2 cells against H2O2-induced oxidative stress by reducing ROS accumulation, modulating redox-related enzymes (Superoxide dismutase, Catalase, Glutathione peroxidase), and alleviating oxidative damage. Notably, HFPS upregulated the expression of antioxidant-related genes, including B-cell lymphoma-2 (Bcl-2), heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2), while downregulating pro-apoptotic genes like Bcl-2-associated X protein (Bax) and Caspase-3. These findings suggest that HFPS exerts its antioxidant effects by modulating the Nrf2/HO-1 pathway and redox homeostasis. This study contributes to the understanding of the structure-function relationships and antioxidant mechanisms of HFPS, highlighting its potential applications as a natural antioxidant in various fields.

The Effect of a Secondary Stressor on the Morphology and Membrane Structure of an Already Challenged Maternal and Foetal Red Blood Cell Population.

The red blood cell (RBC) membrane is unique and crucial for maintaining structural-functional relationships. Maternal smoking induces significant changes in the morphological, rheological, and functional parameters of both maternal and foetal RBCs, mainly due to the continuous generation of the free radicals. The major aim of this study was to follow the consequences of a secondary stressor, like fungal infection, on the already compromised RBC populations. The impact of Candida infection, a growing health concern, was investigated on four blood sample groups: mothers and their neonates originating from non-smoking versus smoking populations. Here, we searched for phenotypical and molecular markers that precisely reflected the effect of Candida infection on the RBC membrane; this included the level of hemolysis, appearance of morphological variants, formation of the lipid peroxidation marker 4-hydroxyl-nonenal, arrangement of the Band 3 molecules and activation of the Caspase 3. In most of the examined cases, the fungal infection increased the adverse symptoms induced by smoking, indicating a general stress response, likely due to an altered redox state of the cells. However, we were able to identify an atypical phenotype (clustered populations with shrinkage and membrane blebbing) in both the non-smoking and smoking populations, which might be a unique marker for Candida spp. infection.

Structure-functionality relationship and modification strategies of oat protein: Challenges and opportunities.

The increasing preference for plant-based proteins over animal-derived equivalents has intensified research into alternative protein sources, with oats emerging as a noteworthy specialty crop due to their rich array of functional and bioactive components. Despite the growing interest, research into oat proteins remains in its early stages, particularly in understanding the structure-function relationship and modification strategies within food systems. Designing novel food products using oat protein presents both opportunities and challenges; the compact quaternary structure and high thermal stability of oat globulin limit its functionality in diverse applications. This review aims to detail the composition and structural characteristics of oat protein, highlighting the complex relationship between these structural traits and their functional properties. A significant focus is placed on innovative structural modification techniques that enable the cost-effective transformation of oat protein into a functional ingredient or base for new food product development.

Autoclaved Starch: Structure and Functionality Relationship in a Matrix With the Same Contribution ofAmylose and Amylopectin.

The rational use of autoclaved starches in food applications is difficult because there is a lack of information on their structure-functionality relationship. The novelty of this research relies on disclosing such an association. Hylon V starch was autoclaved at 105, 120, and 135°C to investigate its crystalline and double-helical features and its relationship with functionality. In autoclaved Hylon V starch, interactions of amylopectin and amylose improved while the crystalline regions decreased. The degree of double helices (DD) decreased after autoclaving at 105°C and the degree of order (DO) increased after treatment at 120 and 135°C. The water solubility index (WSI) (4.63-6.38%) and swelling power (SP) (4.39-7.1 g/g) increased when the temperature increased. On the other hand, water (103.49-225.01%) and oil (61.91-94.53%) holding capacity (WHC and OHC, respectively) increased after autoclaving treatment, although the values decreased with the treatment intensity. The functional properties were affected when the structure changed as a function of the treatment temperatures. PCA analysis showed that WSI and SP of autoclaved Hylon V starch were associated with a high DD, with better compaction, and with stronger amylopectin-amylose interactions. WHC and OHC were associated with better crystallinity, stronger interactions of amylopectin and amylose, and heterogeneous double-helical crystallites. These findings are useful for understanding the structure-functionality relationship of autoclaved Hylon V starch and pave the way for future research regarding the effects of its incorporation on the properties of food matrices such as bread, yogurt, cakes, and pudding.

Sorghum starch: Composition, structure, functionality, and strategies for its improvement

AbstractSorghum (Sorghum bicolor L. Moench) is increasingly recognized as a resilient and climate‐adaptable crop that holds significant potential to enhance global food security sustainably. Compared to other common cereal grains, sorghum boasts a more diverse nutritional profile. The starch component accounts for more than 80% of total sorghum grain weight. Sorghum starch functionality and diverse industrial applications are determined by its physiochemical properties, including pasting, gelatinization, retrogradation, texture, and digestion kinetics. This review provides a comprehensive evaluation of the morphology, minor composition, crystalline structure, fine molecular structure, and structure–function relationships of sorghum starch. It further explores how these properties can be optimized through chemical, physical and enzymatic modifications to extend the applications of sorghum starch. Additionally, the review highlights the role of key enzymes in the biosynthesis of sorghum starch and discusses how biological modifications, enabled by advanced genetic and molecular breeding strategies, can modify starch quality. This review also provides a foundation for developing tailored sorghum varieties with enhanced starch properties that can expand applications of sorghum both in food and non‐food industries, potentially contributing to global food security and sustainable agriculture.

Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization.

The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites. Through mechanisms not fully understood, expression of viroporins facilitates virion assembly/release from infected cells, and subverts the cell physiology, contributing to cytopathogenicity. Compounds that interact with viroporins and interfere with their membrane-permeabilizing activity in vitro, are known to inhibit virus production. Moreover, viroporin-defective viruses comprise a source of live attenuated vaccines that prevent infection by notorious human and livestock pathogens. This review dives into the origin and evolution of the viroporin concept, summarizes some of the methodologies used to characterize the structure-function relationships of these important virulence factors, and attempts to classify them on biophysical grounds attending to their mechanisms of ion/solute transport across membranes.

Disruption of a potential disulfide bond of Cys65-Cys141 on the structure and stability of globin X from zebrafish.

Globin X is a newly discovered member of the globin family, while its structure and function are not fully understood. In this study, we performed protein modelling studies using Alphafold3 and molecular dynamics simulations, which suggested that the protein adopts a typical globin fold, with the formation of a potential disulfide bond of Cys65 and Cys141. To elucidate the role of this unique disulfide in protein structure and stability, we constructed a double mutant of C65S/C141S by mutating the two cysteine residues to serine. As suggested by protein mass, ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopy analyses, the potential disulfide bond has minimal effect on the overall protein structure, but its absence reduces the protein stability. Electron paramagnetic resonance (EPR) analysis also revealed an increase in the proportion of high-spin state heme iron, which accelerates the rate of heme degradation in reaction with H2O2. This study highlights the critical role of the Cys65-Cys141 in maintaining the stability of globin X and the bis-His heme coordination state, providing insights into the structure-function relationship of the newly discovered globin.

Revealing the diverse electrochemistry of nanoparticles with scanning electrochemical cell microscopy.

The next generation of electroactive materials will depend on advanced nanomaterials, such as nanoparticles (NPs), for improved function and reduced cost. As such, the development of structure-function relationships for these NPs has become a prime focus for researchers from many fields, including materials science, catalysis, energy storage, photovoltaics, environmental/biomedical sensing, etc. The technique of scanning electrochemical cell microscopy (SECCM) has naturally positioned itself as a premier experimental methodology for the investigation of electroactive NPs, due to its unique capability to encapsulate individual, spatially distinct entities, and to apply a potential to (and measure the resulting current of) single-NPs. Over the course of conducting these single-NP investigations, a number of unexpected (i.e. rarely-reported) results have been collected, including fluctuating current responses, and carrying of the NP by the SECCM probe, hypothesised to be due to insufficient NP-surface interaction. Additionally, locations with measurable electrochemical activity have been found to contain no associated NP, and conversely locations with no activity have been found to contain NPs. Through presenting and discussing these findings, this article seeks to highlight complications in single-NP SECCM experiments, particularly those arising from issues with sample preparation.

Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects.

Nitrite (NO2-) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO2- and Hb(III)-NO2-), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO2- to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O2 supply to poorly oxygenated tissues, such as the eye's retina. Further, NO2- interacts with Mb(II)-O2 and Hb(II)-O2, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO2- through the O-nitrito binding mode (i.e., Fe-ONO-), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O-), like in most other heme-proteins. The structure-function relationships of the interaction of NO2- with both ferric and ferrous forms of Mb and Hb are discussed here.

Polysaccharide biocomposites with tunable adsorption and antipathogen activity via surface immobilization of chitosan onto modified flax fibers

Flax fiber modified composite (FFMC) duplex systems with unique sorbent and antipathogen properties were developed by physisorption of chitosan onto modified flax fibers by a facile method. Complementary characterization of the FFMCs (Raman, NMR, and IR, SEM, XRD, TGA and BET analysis) revealed variable composite morphology with incremental chitosan doping and supramolecular interactions between the fiber substrate and immobilized chitosan. Dye adsorption profiles of FFMCs with Rose Bengal corroborated the role of physisorption with an adsorption capacity that rises to 17.9 mg/g, whereas the water sorption capacity reaches an impressive value ca. 11 g/g, which indicated the role of synergism upon chitosan immobilization. Anti-microbial and fungal properties were supported by antimicrobial tests. The FFMCs have high antimicrobial potency toward gram negative (E. coli), gram positive (Streptococcus aureus) and a fungal strain (Candida albicans) based on the low FFMC dosages required to achieve 100 % microbial elimination. This versatile class of unique biocomposites displayed unique structure-function relationships related to synergistic water sorption and antipathogenic effects, as compared to available literature reports. FFMCs are a diversiform class of biocomposites with unique physicochemical and biological properties that extend the field of adsorption science and technology from environmental remediation to biomedical devices.