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Cells Nov 2018Aquaporins (AQPs) function as tetrameric structures in which each monomer has its own permeable pathway. The combination of structural biology, molecular dynamics... (Review)
Review
Aquaporins (AQPs) function as tetrameric structures in which each monomer has its own permeable pathway. The combination of structural biology, molecular dynamics simulations, and experimental approaches has contributed to improve our knowledge of how protein conformational changes can challenge its transport capacity, rapidly altering the membrane permeability. This review is focused on evidence that highlights the functional relationship between the monomers and the tetramer. In this sense, we address AQP permeation capacity as well as regulatory mechanisms that affect the monomer, the tetramer, or tetramers combined in complex structures. We therefore explore: (i) water permeation and recent evidence on ion permeation, including the permeation pathway controversy-each monomer versus the central pore of the tetramer-and (ii) regulatory mechanisms that cannot be attributed to independent monomers. In particular, we discuss channel gating and AQPs that sense membrane tension. For the latter we propose a possible mechanism that includes the monomer (slight changes of pore shape, the number of possible H-bonds between water molecules and pore-lining residues) and the tetramer (interactions among monomers and a positive cooperative effect).
PubMed: 30423856
DOI: 10.3390/cells7110209 -
Polymers Aug 2022A molecularly imprinted polymer (MIP) is a synthetic polymer that has characteristics such as natural receptors which are able to interact and bind to a specific... (Review)
Review
A molecularly imprinted polymer (MIP) is a synthetic polymer that has characteristics such as natural receptors which are able to interact and bind to a specific molecule that is used as a template in the MIP polymerization process. MIPs have been widely developed because of the need for more selective, effective, and efficient methods for sample preparation, identification, isolation, and separation. The MIP compositions consist of a template, monomer, crosslinker, initiator, and porogenic solvent. Generally, MIPs are only synthesized using one type of monomer (mono-functional monomer); however, along with the development of MIPs, MIPs began to be synthesized using two types of monomers to improve the performance of MIPs. MIPs used for identification, separation, and molecular analysis have the most applications in solid-phase extraction (SPE) and as biochemical sensors. Until now, no review article has discussed the various studies carried out in recent years in relation to the synthesis of dual-functional monomer MIPs. This review is necessary, as an improvement in the performance of MIPs still needs to be explored, and a dual-functional monomer strategy is one way of overcoming the current performance limitations. In this review article, we discuss the techniques commonly used in the synthesis of dual-functional monomer MIPs, and the use of dual-functional monomer MIPs as sorbents in the MI-SPE method and as detection elements in biochemical sensors. The application of dual-functional monomer MIPs showed better selectivity and adsorption capacity in these areas when compared to mono-functional monomer MIPs. However, the combination of functional monomers must be selected properly, in order to achieve an effective synergistic effect and produce the ideal MIP characteristics. Therefore, studies regarding the synergistic effect of the MIP combination still need to be carried out to obtain MIPs with superior characteristics.
PubMed: 36080573
DOI: 10.3390/polym14173498 -
Frontiers in Pharmacology 2021The clinical and experimental study into the effects of Chinese herbal medicines on chronic kidney disease has evolved over the past 40 years with new insight into... (Review)
Review
The clinical and experimental study into the effects of Chinese herbal medicines on chronic kidney disease has evolved over the past 40 years with new insight into their mechanism and evidence of their clinical effects. Among the many traditional Chinese herbs examined in chronic renal disease, five were found to have evidence of sufficient clinical efficacy, high frequency of use, and well-studied mechanism. They are: and , and its components (tanshinone II A, salvianolic acid A and B); and its monomer ; and its components (triptolide, tripterygium glycosides); Kudzu root and its monomer . These Chinese herbal medications have pharmaceutical effects against fibrosis, inflammation and oxidative stress and also promote renal repair and regeneration. This article reviews their clinical efficacy, anti-fibrotic effects in animal models, and molecular mechanism of action.
PubMed: 34803715
DOI: 10.3389/fphar.2021.774414 -
Journal of Analytical Methods in... 2021Volatile acetone is a potential biomarker that is elevated in various disease states. Measuring acetone in exhaled breath is complicated by the fact that the molecule...
BACKGROUND
Volatile acetone is a potential biomarker that is elevated in various disease states. Measuring acetone in exhaled breath is complicated by the fact that the molecule might be present as both monomers and dimers, but in inconsistent ratios. Ignoring the molecular form leads to incorrect measured concentrations. Our first goal was to evaluate the monomer-dimer ratio in ambient air, critically ill patients, and rats. Our second goal was to confirm the accuracy of the combined (monomer and dimer) analysis by comparison to a reference calibration system.
METHODS
Volatile acetone intensities from exhaled air of ten intubated, critically ill patients, and ten ventilated Sprague-Dawley rats were recorded using ion-mobility spectrometry. Acetone concentrations in ambient air in an intensive care unit and in a laboratory were determined over 24 hours. The calibration reference was pure acetone vaporized by a gas generator at concentrations from 5 to 45 ppb (parts per billion by volume).
RESULTS
Acetone concentrations in ambient laboratory air were only slightly greater (5.6 ppb; 95% CI 5.1-6.2) than in ambient air in an intensive care unit (5.1 ppb; 95% CI 4.4-5.5; < 0.001). Exhaled acetone concentrations were only slightly greater in rats (10.3 ppb; 95% CI 9.7-10.9) than in critically ill patients (9.5 ppb; 95% CI 7.9-11.1; < 0.001). Vaporization yielded acetone monomers (1.3-5.3 mV) and dimers (1.4-621 mV). Acetone concentrations (ppb) and corresponding acetone monomer and dimer intensities (mV) revealed a high coefficient of determination ( = 0.96). The calibration curve for acetone concentration (ppb) and total acetone (monomers added to twice the dimers; mV) was described by the exponential growth 3-parameter model, with an = 0.98.
CONCLUSION
The ratio of acetone monomer and dimer is inconsistent and varies in ambient air from place-to-place and across individual humans and rats. Monomers and dimers must therefore be considered when quantifying acetone. Combining the two accurately assesses total volatile acetone.
PubMed: 34395017
DOI: 10.1155/2021/6638036 -
Frontiers in Chemistry 2022In this work, urushiol-based polybenzoxazine is cured by the Lewis acid (FeCl, AlCl and CuCl) at low temperature instead of high thermal curing temperature. The effect...
In this work, urushiol-based polybenzoxazine is cured by the Lewis acid (FeCl, AlCl and CuCl) at low temperature instead of high thermal curing temperature. The effect of the Lewis acid on structures and properties of the polymers is revealed. The relating urushiol-based benzoxazine monomer (BZ) was synthesized by natural urushiol, formaldehyde, and -octylamine. The monomer was reacted with the Lewis acid with a molar ratio of 6:1 (N: N) at 80°C to obtain films that can be cured at room temperature. The chemical structures of benzoxazine monomers were identified by Fourier-transform infrared spectroscopy (FTIR) and H nuclear magnetic resonance spectroscopy (H-NMR). The interaction between the metal ion and the polymers is revealed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance-FTIR (ATR-FTIR). The effect of the Lewis acid on the mechanical properties, wettability, and thermal stability was investigated. The results show that the benzoxazine cured by Cu has a better performance than that cured by Al and Fe.
PubMed: 35572108
DOI: 10.3389/fchem.2022.879605 -
Journal of Cell Science Jan 2018Globular (G)-actin, the actin monomer, assembles into polarized filaments that form networks that can provide structural support, generate force and organize the cell.... (Review)
Review
Globular (G)-actin, the actin monomer, assembles into polarized filaments that form networks that can provide structural support, generate force and organize the cell. Many of these structures are highly dynamic and to maintain them, the cell relies on a large reserve of monomers. Classically, the G-actin pool has been thought of as homogenous. However, recent work has shown that actin monomers can exist in distinct groups that can be targeted to specific networks, where they drive and modify filament assembly in ways that can have profound effects on cellular behavior. This Review focuses on the potential factors that could create functionally distinct pools of actin monomers in the cell, including differences between the actin isoforms and the regulation of G-actin by monomer binding proteins, such as profilin and thymosin β4. Owing to difficulties in studying and visualizing G-actin, our knowledge over the precise role that specific actin monomer pools play in regulating cellular actin dynamics remains incomplete. Here, we discuss some of these unanswered questions and also provide a summary of the methodologies currently available for the imaging of G-actin.
Topics: Actins; Animals; Cytoskeleton; Humans; Kinetics; Models, Molecular; Profilins; Thymosin
PubMed: 29321224
DOI: 10.1242/jcs.203760 -
Progress in Biophysics and Molecular... Sep 2017In domain-swapping, two or more identical protein monomers exchange structural elements and fold into dimers or multimers whose units are structurally similar to the... (Review)
Review
In domain-swapping, two or more identical protein monomers exchange structural elements and fold into dimers or multimers whose units are structurally similar to the original monomer. Domain-swapping is of biotechnological interest because inhibiting domain-swapping can reduce disease-causing fibrillar protein aggregation. To achieve such inhibition, it is important to understand both the energetics that stabilize the domain-swapped structure and the protein dynamics that enable the swapping. Structure-based models (SBMs) encode the folded structure of the protein in their potential energy functions. SBMs have been successfully used to understand diverse aspects of monomer folding. Symmetrized SBMs model interactions between two identical protein chains using only intra-monomer interactions. Molecular dynamics simulations of such symmetrized SBMs have been used to correctly predict the domain-swapped structure and to understand the mechanism of domain-swapping. Here, we review such models and illustrate that monomer topology determines key aspects of domain-swapping. However, in some proteins, specifics of local energetic interactions modulate domain-swapping and these need to be added to the symmetrized SBMs. We then summarize some general principles of the mechanism of domain-swapping that emerge from the symmetrized SBM simulations. Finally, using our own results, we explore how symmetrized SBMs could be used to design domain-swapping in proteins.
Topics: Models, Molecular; Protein Domains; Protein Folding; Proteins
PubMed: 27867057
DOI: 10.1016/j.pbiomolbio.2016.09.013 -
Cardiovascular Research Jul 2023A key event in the regulation of cardiac contraction and relaxation is the phosphorylation of phospholamban (PLN) that relieves the inhibition of the sarco/endoplasmic...
AIMS
A key event in the regulation of cardiac contraction and relaxation is the phosphorylation of phospholamban (PLN) that relieves the inhibition of the sarco/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). PLN exists in an equilibrium between monomers and pentamers. While only monomers can inhibit SERCA2a by direct interaction, the functional role of pentamers is still unclear. This study investigates the functional consequences of PLN pentamerization.
METHODS AND RESULTS
We generated transgenic mouse models expressing either a PLN mutant that cannot form pentamers (TgAFA-PLN) or wild-type PLN (TgPLN) in a PLN-deficient background. TgAFA-PLN hearts demonstrated three-fold stronger phosphorylation of monomeric PLN, accelerated Ca2+ cycling of cardiomyocytes, and enhanced contraction and relaxation of sarcomeres and whole hearts in vivo. All of these effects were observed under baseline conditions and abrogated upon inhibition of protein kinase A (PKA). Mechanistically, far western kinase assays revealed that PLN pentamers are phosphorylated by PKA directly and independent of any subunit exchange for free monomers. In vitro phosphorylation of synthetic PLN demonstrated that pentamers even provide a preferred PKA substrate and compete with monomers for the kinase, thereby reducing monomer phosphorylation and maximizing SERCA2a inhibition. However, β-adrenergic stimulation induced strong PLN monomer phosphorylation in TgPLN hearts and sharp acceleration of cardiomyocyte Ca2+ cycling and haemodynamic values that now were indistinguishable from TgAFA-PLN and PLN-KO hearts. The pathophysiological relevance of PLN pentamerization was evaluated using transverse aortic constriction (TAC) to induce left ventricular pressure overload. Compared to TgPLN, TgAFA-PLN mice demonstrated reduced survival after TAC, impaired cardiac haemodynamics, failure to respond to adrenergic stimulation, higher heart weight, and increased myocardial fibrosis.
CONCLUSIONS
The findings show that PLN pentamerization greatly impacts on SERCA2a activity as it mediates the full range of PLN effects from maximum inhibition to full release of SERCA2a function. This regulation is important for myocardial adaptation to sustained pressure overload.
Topics: Mice; Animals; Calcium; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Calcium-Binding Proteins; Myocytes, Cardiac; Mice, Transgenic; Phosphorylation; Cyclic AMP-Dependent Protein Kinases; Adrenergic Agents; Sarcoplasmic Reticulum
PubMed: 36869774
DOI: 10.1093/cvr/cvad037 -
ACS Sustainable Chemistry & Engineering Apr 2024The cross-linked nature of vulcanized rubbers as used in tire and many other applications prohibits an effective closed-loop mechanical or chemical recycling. Moreover,...
The cross-linked nature of vulcanized rubbers as used in tire and many other applications prohibits an effective closed-loop mechanical or chemical recycling. Moreover, vulcanization significantly retards the material's biodegradation. Here, we report a recyclable and biodegradable rubber that is generated by the vulcanization of amorphous, unsaturated polyesters. The elastic material can be broken down solvolysis into the underlying monomers. After removal of the vulcanized repeat units, the saturated monomers, constituting the major share of the material, can be recovered in overall recycling rates exceeding 90%. Respirometric biodegradation experiments by CO tracking under environmental conditions the polyesters' diol monomer indicated depolymerization and partial mineralization of the vulcanized polyester rubbers.
PubMed: 38665800
DOI: 10.1021/acssuschemeng.3c08435 -
Journal of Biomedical Optics Jul 2021Collagen is the most abundant protein in vertebrates and is found in tissues that regularly experience tension, compression, and shear forces. However, the underlying...
SIGNIFICANCE
Collagen is the most abundant protein in vertebrates and is found in tissues that regularly experience tension, compression, and shear forces. However, the underlying mechanism of collagen fibril formation and remodeling is poorly understood.
AIM
We explore how a collagen monomer is visualized using fluorescence microscopy and how its spatial orientation is determined. Defining the orientation of collagen monomers is not a trivial problem, as the monomer has a weak contrast and is relatively small. It is possible to attach fluorescence tags for contrast, but the size is still a problem for detecting orientation using fluorescence microscopy.
APPROACH
We present two methods for detecting a monomer and classifying its orientation. A modified Gabor filter set and an automatic classifier trained by convolutional neural network based on a synthetic dataset were used.
RESULTS
By evaluating the performance of these two approaches with synthetic and experimental data, our results show that it is possible to determine the location and orientation with an error of ∼37 deg of a single monomer with fluorescence microscopy.
CONCLUSIONS
These findings can contribute to our understanding of collagen monomers interaction with collagen fibrils surface during fibril formation and remodeling.
Topics: Animals; Collagen; Extracellular Matrix; Microscopy, Fluorescence; Neural Networks, Computer; Skin
PubMed: 34240588
DOI: 10.1117/1.JBO.26.7.076501