Mode Of Dimerization Research Articles

TRIM35 ubiquitination regulates the expression of PKM2 tetramer and dimer and affects the malignant behaviour of breast cancer by regulating the Warburg effect.

Breast cancer has become the leading cause of death in females. After comprehensive treatment, the lives of patients are still threatened by tumor metastasis and recurrence. Therefore, there is an urgent requirement to find an effective treatment target for breast cancer. Tripartite motif-containing 35 (TRIM35) is a ubiquitin ligase that has an important role in the recurrence and metastasis of malignant tumors. However, the role of TRIM35 in breast cancer has thus far remained elusive. The expression of TRIM35 was examined in a bioinformatics database and the effects of TRIM35 on the malignant biological behavior of breast cancer were analyzed by Cell Counting Kit-8, cell migration and invasion assays, flow cytometry and nude mouse xenograft experiments. It was determined that TRIM35 was downregulated in breast cancer tumor tissues and cell lines. Patients with low TRIM35 expression had shorter overall survival. Functional assays revealed that overexpression of TRIM35 inhibited the proliferation, migration and invasion, and promoted apoptosis of breast cancer cells. Furthermore, overexpression of TRIM35 was able to inhibit the Warburg effect in breast cancer cells. Mechanistic analyses indicated that TRIM35 regulates the transition of tetramers and dimers of pyruvate kinase M2 (PKM2) through ubiquitination and thereby affects the Warburg effect. In conclusion, the present results indicated that TRIM35 regulates the tetramer and dimer transition of PKM2 through ubiquitination and affects the malignant biological behavior of breast cancer by modulating the Warburg effect.

Assessing the Experimental Hydrogen Bonding Energy of the Cyclic Water Dimer Transition State with a Cyclooctatetraene-Based Molecular Balance.

We have conducted an experimental and computational study of cyclooctatetraene-1,4/1,6-dimethanol (1,4 and 1,6) as a molecular balance with the goal in mind to determine the otherwise inaccessible hydrogen bonding energy (HBE) of the cyclic water dimer, which constitutes a transition state. The 1,4/1,6 folding equilibrium is governed by an intramolecular hydrogen bond in the folded 1,6-isomer, in which the OH groups adopt a cyclic planar geometry, akin to the structure of the cyclic water dimer transition state. We characterized hydrogen bonding in 1,6 and reference complexes utilizing SAPT2 + (3)δMP2/aug-cc-pVTZ and selected quantum theory of atoms in molecule descriptors at M06-2XD3(0)/ma-def2-TZVPP. Additionally, we computed HBEs at the DLPNO-CCSD(T)/aug-cc-pVQZ level of theory. We find that hydrogen bonding in 1,6 is very similar to the interaction in the Ci symmetric cyclic water dimer TS, both in magnitude and character. We experimentally determined the Gibbs free energy of the folding process (ΔGeq) in a variety of organic solvents via nuclear magnetic resonance spectroscopy measurements at room temperature. By combining experimentally obtained ΔGeq values with corrections derived from accurate computational methods, we provide estimates for the HBE of cyclic water dimers and the cyclic water dimer TS, as the most stable cyclic water dimer.

Emission spectra of argon and hydrogen excited by pulses with durations of 0.7 and 160 ns in an inhomogeneous electric field

In this paper, the radiation of argon and hydrogen in a repetitively pulsed diffuse discharge formed in an inhomogeneous electric field at elevated gas pressure have been studied. The emission spectra are measured under a series of short voltage pulses with the durations of 0.7 ns and 160 ns. It is shown that for the diffuse discharge in pure argon, the transition of argon dimers (Ar2*, λ max = 126 nm) have the highest intensity. Small addition of Xe to Ar contributes to the disappearance of Ar2* radiation bands and the appearance of those of ArXe* and Xe2* dimers in the plasma emission spectrum. In hydrogen, emission at the maximum wavelength of 160 nm is dominated in the spectra of the diffuse discharge and the luminescence intensity in the region of 220–280 nm is relatively low. If Ar is added to H2, the diffuse discharge behaves non-uniform. The luminescence band with the peak at 160 nm narrows, strong argon ion line (Ar+, λ max = 191 nm) appears in the spectra, and the luminescence in the spectral region 220–280 nm reappears. The excitation temperature and electron density are diagnosed using emission spectra and images of the discharge plasma. It is shown that both of the excitation temperature and electron density increase as the electric field is enhanced, while the excitation temperature decreases as the gas pressure increases.

An N-N linked dimeric indole alkaloid from the marine sponge-associated rare actinomycetes Kocuria sp. S42

Marine derived rare actinomycetes is emerging as one of the new sources for various natural products for further drug discovery. Dimeric indole alkaloids represent a group of structurally diverse natural products and N-N linkage is a special dimerization mode. Here, we report the isolation of 1,1'-([1,1'-biindole]-3,3'-diyl) bis (ethane-1,2-diol), a new tryptophan-derived indole alkaloid from the marine sponge-derived Kocuria sp. S42. The structure was established based on extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. The new dimeric indole alkaloid via N-N linkage exhibits moderate antimicrobial activity.

Interpretation of Ir L -edge isotropic x-ray absorption spectra across the pressure-induced dimerization transition in hyperhoneycomb β−Li2IrO3

The extended nature of atomic $5d$ orbitals, together with a relatively short $\ensuremath{\sim}3\phantom{\rule{0.16em}{0ex}}\AA{}$ Ir-Ir distance across edge-shared octahedra in honeycomb iridate lattices, leads to a tendency to disrupt the local, spin-orbit-entangled ${j}_{\mathrm{eff}}=\frac{1}{2}$ moments of ${\mathrm{Ir}}^{4+}$ ions in favor of dimerization and the formation of molecular orbitals, especially upon lattice compression. The sensitivity of Ir $L$-edge spectroscopy to both spin-orbit entanglement in ${j}_{\mathrm{eff}}$ states and the quenching of orbital degrees of freedom in dimerized states results in a peculiar evolution of x-ray absorption spectra across dimerization transitions, including energy shifts in the opposite direction for ${L}_{3}$ and ${L}_{2}$ leading absorption edges and substantial changes in their isotropic branching ratio. We present a theoretical description of the evolution of $5d$ electronic states, and related x-ray absorption spectra, in going from the single ion to the dimerized limit. The calculations reproduce the experimental results for hyper-honeycomb $\ensuremath{\beta}\text{\ensuremath{-}}{\mathrm{Li}}_{2}{\mathrm{IrO}}_{3}$ [L. Veiga et al., Phys. Rev. B 100, 064104 (2019); L. Veiga et al., Phys. Rev. B 96, 140402(R) (2017)] and shed light into the weakening of the coupling between spin and orbital degrees of freedom as the strength of dimerization increases. The results provide a basis for the interpretation of $L$-edge x-ray absorption spectra in $5d$ systems where competition between the formation of local ${j}_{\mathrm{eff}}$ states and molecular orbitals is at play.

C–H⋯S Hydrogen Bond Assisted Supramolecular Encapsulation of Fullerenes with Nanobelts

C–H⋯S Hydrogen Bond Assisted Supramolecular Encapsulation of Fullerenes with Nanobelts

In silico insights into the dimer structure and deiodinase activity of type III iodothyronine deiodinase from bioinformatics, molecular dynamics simulations, and QM/MM calculations

The homodimeric family of iodothyronine deiodinases (Dios) regioselectively remove iodine from thyroid hormones. Currently, structural data has only been reported for the monomer of the mus type III thioredoxin (Trx) fold catalytic domain (Dio3Trx), but the mode of dimerization has not yet been determined. Various groups have proposed dimer structures that are similar to the A-type and B-type dimerization modes of peroxiredoxins. Computational methods are used to compare the sequence of Dio3Trx to related proteins known to form A-type and B-type dimers. Sequence analysis and in silico protein-protein docking methods suggest that Dio3Trx is more consistent with proteins that adopt B-type dimerization. Molecular dynamics (MD) simulations of the refined Dio3Trx dimer constructed using the SymmDock and GalaxyRefineComplex databases indicate stable dimer formation along the β4α3 interface consistent with other Trx fold B-type dimers. Free energy calculations show that the dimer is stabilized by interdimer interactions between the β-sheets and α-helices. A comparison of MD simulations of the apo and thyroxine-bound dimers suggests that the active site binding pocket is not affected by dimerization. Determination of the transition state for deiodination of thyroxine from the monomer structure using QM/MM methods provides an activation barrier consistent with previous small model DFT studies. Communicated by Ramaswamy H. Sarma

Integrating Photorewritable Fluorescent Information in Shape‐Memory Organohydrogel Toward Dual Encryption

AbstractAs one of the severe global problems, counterfeiting information has brought a huge negative impact on every aspect of human society. Though various anticounterfeiting strategies, including fluorescent materials, are widely developed for dealing with the above problem, the information security level needs to be further improved due to sophisticated hacking techniques. In this study, an organohydrogel is designed by constructing interpenetrating organohydrogel networks, in which naphthalimide moieties (DEAN, green‐yellow emission) are introduced in hydrophilic poly(N,N‐dimethylacrylamide) (PDMA) hydrogel network and anthracene units (blue emission) are copolymerized in hydrophobic polystearate methacrylate (PSMA) organogel network. Triggered by UV light of 365 nm, the unimer–dimer transition occurs and leads the fluorescent color of organohydrogel to change from blue to faint yellow, making secret information be stored with the assistance of photomasks. Furthermore, by combining crystallization‐induced shape memory performance, dual encryption can be achieved. This fluorescent organohydrogel provides a new idea for fabricating smart materials with the ability of encryption–decryption, which is of great significance in information security protection.

Chiral Water-Soluble Molecular Capsules With Amphiphilic Interiors.

We present the synthesis of new chiral water-soluble dimeric capsules by the multicomponent Mannich reaction between charged amino acids (glutamic acid or arginine), resorcinarene, and formaldehyde and by subsequent self-assembly. The zwitterionic character of the backbones enables electrostatic interactions between arms and induces self-assembly of dimeric capsules, namely, (L-ArgR)2 and (L-GluR)2, in water with a wide range of pH, as demonstrated by NMR, diffusion coefficient measurement, and circular dichroism. The assembly/disassembly processes are fast on the NMR timescale. This mode of dimerization leaves side chains available for additional interactions and creates chiral cavities of mixed hydrophobic/hydrophilic character. According to this characteristic, capsules do not bind fully nonpolar or fully polar guests but effectively encapsulate a variety of chiral molecules with mixed polar/apolar characters (aliphatic and aromatic aldehydes, epoxides, alcohols, carboxylic acids, amines, and amino acids) with moderate strength. We also demonstrate the formation of heterocapsules (GluR) (ArgR) (homo- and heterochiral) that utilize additional interactions between charged acidic and basic side chains and have better encapsulation properties than those of the homodimers.

Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans

The JmjC family of 2-oxoglutarate dependent oxygenases catalyse a range of hydroxylation and demethylation reactions in humans and other animals. Jumonji domain-containing 7 (JMJD7) is a JmjC (3S)-lysyl-hydroxylase that catalyses the modification of Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1 and 2); JMJD7 has also been reported to have histone endopeptidase activity. Here we report biophysical and biochemical studies on JMJD7 from Drosophila melanogaster (dmJMJD7). Notably, crystallographic analyses reveal that the unusual dimerization mode of JMJD7, which involves interactions between both the N- and C-terminal regions of both dmJMJD7 monomers and disulfide formation, is conserved in human JMJD7 (hsJMJD7). The results further support the assignment of JMJD7 as a lysyl hydroxylase and will help enable the development of selective inhibitors for it and other JmjC oxygenases.

Biochemical and subcellular characterization of a squid hnRNPA/B-like protein 2 in osmotic stress activated cells reflects molecular properties conserved in this protein family.

We have identified endogenous p65 to be an SDS-stable dimer protein composed of ~ 37kDa hnRNPA/B-like subunits. We have investigated molecular properties involved in the stability of dimeric form, and their regulation in the transition between monomeric and dimeric forms of hnRNPA/B-like protein 2. We also investigated a cellular property conserved between squid hnRNPA/B-like protein 2 and human hnRNPA1 protein in a neuronal context. Here we show biochemical properties of a recombinant hnRNPA/B-like protein 2 (rP2) in vitro experiments, as one of p65 subunit. We found that interaction between rP2 and RNA molecules interfered with the dynamics of rP2 dimers formation, involved in disulfide bonds and/or postranslational alterations in distinct stage of SDS-stable dimers formation. In addition, we have performed immunofluorescence in SH-SY5Y cells and observed that the pEGFP-P2 fusion protein was expressed in the nucleus, similar to what is observed for human hnRNPA1 protein. Our results reinforce the idea that p65 is an SDS-stable dimer. Thus, a deeper understanding between monomeric and dimeric transition dynamic is critical into evolution of several neurodegenerative disease.

Approach to Study pH-Dependent Protein Association Using Constant-pH Molecular Dynamics: Application to the Dimerization of β-Lactoglobulin.

Protein-protein association is often mediated by electrostatic interactions and modulated by pH. However, experimental and computational studies have often overlooked the effect of association on the protonation state of the protein. In this work, we present a methodological approach based on constant-pH molecular dynamics (MD), which aims to provide a detailed description of a pH-dependent protein-protein association, and apply it to the dimerization of β-lactoglobulin (BLG). A selection of analyses is performed using the data generated by constant-pH MD simulations of monomeric and dimeric forms of bovine BLG, in the pH range 3-8. First, we estimate free energies of dimerization using a computationally inexpensive approach based on the Wyman-Tanford linkage theory, calculated in a new way through the use of thermodynamically based splines. The individual free energy contribution of each titratable site is also calculated, allowing for identification of relevant residues. Second, the correlations between the proton occupancies of pairs of sites are calculated (using the Pearson coefficient), and extensive networks of correlated sites are observed at acidic pH values, sometimes involving distant pairs. In general, strongly correlated sites are also slow proton exchangers and contribute significantly to the pH-dependency of the dimerization free energy. Third, we use ionic density as a fingerprint of protein charge distribution and observe electrostatic complementarity between the monomer faces that form the dimer interface, more markedly at the isoionic point (where maximum dimerization occurs) than at other pH values, which might contribute to guide the association. Finally, the pH-dependent dimerization modes are inspected using PCA, among other analyses, and two states are identified: a relaxed state at pH 4-8 (with the typical alignment of the crystallographic structure) and a compact state at pH 3-4 (with a tighter association and rotated alignment). This work shows that an approach based on constant-pH MD simulations can produce rich detailed pictures of pH-dependent protein associations, as illustrated for BLG dimerization.

Steric Hindrance Favors σ Dimerization over π Dimerization for Julolidine Dicyanomethyl Radicals.

Metastable radicals exist in a steady-state equilibrium in solution with dimers, which can be either σ dimers or π dimers. Here, we show that steric hindrance at the para position causes julolidine-derived dicyanomethyl radicals to form σ dimers rather than π dimers, the opposite behavior as seen in other carbon-centered radicals, where steric hindrance typically favors pimerization. The change in dimerization mode can be attributed to weaker London dispersion forces and a decreased orbital overlap in the sterically hindered dicyanomethyl radical π dimers, while the bulky groups exert relatively little effect on the energy of the σ dimer.

Histone FRET Microscopy Reveals That Genome Architecture Is Differentially Regulated by a Hp1α Monomer to Dimer Transition

Histone FRET Microscopy Reveals That Genome Architecture Is Differentially Regulated by a Hp1α Monomer to Dimer Transition

Dark modes in symmetric bulk Dirac semimetal dimers excited by cylindrical vector beams

Dark plasmonic modes with sharp spectral resonance peak and exceptionally high quality factor makes it essential for applications in bio-chemical sensing and fluorescence enhancement. Here, we investigate the mid-infrared spectral responses of bulk Dirac semimetal (BDS) dimers under focused azimuthally polarized and radially polarized cylindrical vector beams (CVB). Through numerical simulations, we obtained direct excitation of dark modes and revealed how the beams manipulate the dipole hybridization to produce these modes. By tuning the Fermi energy of BDS, the resonant wavelength of the dark modes can be further adjusted. Our results may find the application of CVB in plasmonic sensing.

Biophysical Investigation of the Interplay between the Conformational Species of Domain-Swapped GB1 Amyloid Mutant through Real-Time Monitoring of Amyloid Fibrillation.

Mutant polypeptide GB1HS#124F26A, which is known to aggregate into amyloid-like fibrils, has been utilized as a model in this study for gaining insights into the mechanism of domain-swapped aggregation through real-time monitoring. Size exclusion with UV monitoring at 280 nm and dynamic light scattering (DLS) profiles through different time points of fibrillation reveal that the dimer transitions into monomeric intermediates during the aggregation, which could further facilitate domain swapping to form amyloid fibrils. The 1D 1H and 2D 1H–13C HSQC nuclear magnetic resonance (NMR) spectra profiling through different time points of fibrillation reveal that there may be some other species present along with the dimer during aggregation which contribute to different trends for the intensity of protons in the spectral peaks. Diffusion NMR reveals changes in the mobility of the dimeric species during the process of aggregation, indicating that the dimer gives rise to other lower molecular weight species midway during aggregation, which further add up to form the oligomers and amyloid fibrils successively. The present work is a preliminary study which explores the possibility of utilizing biophysical methods to gain atomistic level insights into the different stages of aggregation.

Millimeter-Wave Measurements and Applications of Dipole Modes in Spherical Alumina Dimer

Dielectric dimers composed of spherical Alumina ceramic resonators are studied. The electromagnetic scattering of dimer configurations is analyzed through spherical multipole decomposition. Different configurations of dimer operation are addressed with respect to propagation direction and polarization of the incident wave. In context to forward scattering caused by dipole interaction, measurements are performed in V-band (50–75 GHz) to quantify the corresponding electromagnetic signature of the dielectric dimer. Based on the fundamental dipole modes excited in the subwavelength free-space gap along the dimer axis, electric and magnetic hotspots are proposed, which can be exploited for near-field enhancement-based applications at millimeter-wave frequency. A dedicated frequency-scaled measurement setup is designed to measure the field-enhancement factor between 25 and 30 GHz in the free-space dimer gap, corresponding well to simulated results.

Predicting a Kind of Unusual Multiple-States Dimerization-Modes Transformation in Protein PD-L1 System by Computational Investigation and a Generalized Rate Theory.

The new cancer immunotherapy has been carried out with an almost messianic zeal, but its molecular basis remains unclear due to the complexity of programmed death ligand 1 (PD-L1) dimerization. In this study, a new and integral multiple dimerization-modes transformation process of PD-L1s (with a new PD-L1 dimerization mode and a new transformation path discovered) and the corresponding mechanism are predicted using theoretical and computational methods. The results of the state analysis show that 5 stable binding states exist in system. A generalized inter-state transformation rate (GITR) theory is also proposed in such multiple-states self-assembly system to explore the kinetic characteristics of inter-state transformation. A “drug insertion” path was identified as the dominant path of the PD-L1 dimerization-modes transformation. Above results can provide supports for both the relative drug design and other multiple-states self-assembly system from the theoretical chemistry perspective.

Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenetic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as preformed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allow not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs might occur. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.

Soliton dimer–soliton scattering in coupled quasi-one-dimensional dipolar Bose–Einstein condensates

We discuss scattering between a bright soliton and a soliton dimer in coupled quasi-one-dimensional dipolar Bose–Einstein condensates. The dimer is formed by each soliton from both tubes due to the attractive inter-layer dipole–dipole interaction. The dipoles within each tube repel each other, and a stable, bright soliton is stabilized via attractive contact interactions. In general, the scattering is inelastic, transferring the kinetic energy into internal modes of both soliton dimer and single soliton. Our studies reveal rich scattering scenarios, including dimer–soliton repulsion at small initial velocities, exchange of atoms between dimer and single soliton and soliton fusion at intermediate velocities. Interestingly, for some particular initial velocities, the dimer–soliton scattering results in a state of two dimers. At large initial velocities, the scattering is elastic as expected.