Structural Fluctuations Research Articles

Impact of Ring-Closing on the Photophysical Properties of One-Dimensional π-Conjugated Molecular Aggregate.

The self-assembled state of molecules plays a pivotal role in determining how inherent molecular properties transform and give rise to supramolecular functionalities and has long attracted attention. However, understanding the influence of morphologies spanning the nano- to mesoscopic scales of supramolecular assemblies derived from identical intermolecular interactions has been notoriously challenging due to dynamic structural change and monomer exchange of assemblies in solution. In this study, we demonstrate that curved one-dimensional molecular assemblies (supramolecular polymers) of lengths of around 70-200 nm, originating from the same luminescent molecule, exhibit distinct photoluminescent properties when they form closed circular structures (toroids) versus when they possess chain termini in solution (random coils). By exploiting the difference in kinetic stability between the toroids and random coils, we developed a dialysis protocol to selectively purify the former. It was revealed that these terminus-free closed structures manifest higher energy and more efficient luminescence compared with their mixed state with random coils. Time-resolved fluorescence measurements unveiled that random coils, due to their dynamic structural fluctuation in solution, generate local defects throughout the main chain, leading to luminescence from lower energy levels. In mixtures of the two assemblies, luminescence was exclusively observed from such a lower energy level of random coils, a result attributed to energy transfer between the assemblies. This work emphasizes that for identical supramolecular assemblies, only averaged properties have traditionally been considered, but their structures at the nano- to mesoscopic scale are important especially if they have a certain degree of shape persistency even in solution.

Interplay between anion-receptor and anion-solvent interactions in halide receptor complexes characterized with ultrafast infrared spectroscopies.

The competition between host-guest binding and solvent interactions is a crucial factor in determining the binding affinities and selectivity of molecular receptor species. The interplay between these competing interactions, however, have been difficult to disentangle. In particular, the development of molecular-level descriptions of solute-solvent interactions remains a grand experimental challenge. Herein, we investigate the prototypical halide receptor meso-octamethylcalix[4]pyrrole (OMCP) complexed with either chloride or bromide anions in both dichloromethane (DCM) and chloroform (trichloromethane, TCM) solvent using ultrafast infrared transient absorption and 2D IR spectroscopies. OMCP·Br- complexes in both solvents display slower vibrational relaxation dynamics of the OMCP pyrrole NH stretches, consistent with weaker H-bonding interactions with OMCP compared to chloride and less efficient intermolecular relaxation to the solvent. Further, OMCP·Br- complexes show nearly static spectral diffusion dynamics compared to OMCP·Cl-, indicating larger structural fluctuations occur within chloride complexes. Importantly, distinct differences in the vibrational spectra and dynamics are observed between DCM and TCM solutions. The data are consistent with stronger and more perturbative solvent effects in TCM compared to DCM, despite DCM's larger dielectric constant and smaller reported OMCP·X- binding affinities. These differences are attributed to the presence of weak H-bond interactions between halides and TCM, in addition to competing interactions from the bulky tetrabutylammonium countercation. The data provide important experimental benchmarks for quantifying the role of solvent and countercation interactions in anion host-guest complexes.

Frame-by-frame observations of structure fluctuations in single mass-selected Au clusters using aberration-corrected electron microscopy.

The multi-dimensional potential energy surface (PES) of a nanoparticle, such as a bare cluster of metal atoms, controls both the structure and dynamic behaviour of the particle. These properties are the subject of numerous theoretical simulations. However, quantitative experimental measurements of critical PES parameters are needed to regulate the models employed in the theoretical work. Experimental measurements of parameters are currently few in number, while model parameters taken from bulk systems may not be suitable for nanosystems. Here we describe a new measurement methodology, in which the isomer structures of a single deposited nanocluster are obtained frame-by-frame in an aberration-corrected scanning transmission electron microscope (ac-STEM) in high angle annular dark field (HAADF) mode. Several gold clusters containing 309 ± 15 atoms were analysed individually after deposition from a mass-selected cluster source onto an amorphous carbon film. The main isomers identified are icosahedral (Ih), decahedral (Dh) and face-centred-cubic (fcc) (the bulk structure), alongside many amorphous (glassy) structures. The results, which are broadly consistent with static ac-STEM measurements of an ensemble of such clusters, open the way to dynamic measurements of many different nanoparticles of diverse sizes, shapes and compositions.

Comprehensive structural and functional analysis of hVEGFR1: Insights into phosphorylation, molecular interactions, and potential inhibitors through docking and dynamics simulations

Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), is an enzyme with tyrosine kinase activity that plays a pivotal role in angiogenesis, the process of new blood vessel formation. This receptor is of significant clinical importance as it is implicated in various cancers, particularly non-small cell lung cancer (NSCLC), where its dysregulation leads to uncontrolled cell growth through ligand-induced phosphorylation. While commercially available drugs target VEGFR1, their prolonged use often leads to drug resistance and the emergence of mutations in cancer patients. To address these challenges, researchers have identified the human tyrosine kinase (hTK) domain of VEGFR1 as a potential therapeutic marker for lung malignancies. The 3D crystal structure of the hTK domain, obtained from Protein Data Bank (PDB ID: 3HNG), has provided vital structural insights of hVEGFR1. This study has revealed variations within the hVEGFR1 tyrosine kinase domain, distinguishing between regions associated with phosphorylase kinase and transferase activities. We identified numerous potential phosphorylation sites within the TK domain, shedding light on the protein's regulation and signaling possible. Detailed molecular interaction analyses have elucidated the binding forces between lead molecules and hVEGFR1, including hydrogen bonds, electrostatic, hydrophobic, and π-sigma interactions. The stability observed during molecular dynamics simulations further underscores the biological relevance of these interactions. Furthermore, docked complexes has highlighted localized structural fluctuations, offering insight into potential allosteric effects and dynamic conformational changes induced by lead molecules. These findings not only provide a comprehensive characterization of hVEGFR1 but also pave the way for the development of targeted therapies. Eventually, this study has the potential in identifying drug to combat diseases associated with hVEGFR1 dysregulation, including cancer and angiogenesis-related disorders, contributing to effective treatment strategies.

Comparative Analysis of Sibutramine Concentration Determination

This paper underscores the practical implications of employing FTIR RMSE analysis in pharmaceutical research. It highlights the method's rapid and non-destructive nature for quantifying drug concentration in complex formulations, emphasizing its significance in pharmaceutical quality assurance. The study advocates for integrating FTIR RMSE with conventional gravimetric and volumetric methods to enhance the analytical toolkit for pharmaceutical compound analysis. Furthermore, it elucidates the potential of FTIR RMSE in expediting analytical processes and improving estimation accuracy. The paper accentuates the synergy between classical gravimetric techniques and modern spectroscopic methods, providing valuable insights into pharmaceutical compound analysis within heterogeneous formulations. In terms of contributions, this paper advances analytical methods in pharmaceutical research by comprehensively exploring traditional gravimetric/volumetric techniques alongside Fourier Transform Infrared Spectroscopy (FTIR) coupled with Root Mean Square Error (RMSE) analysis. It assesses their effectiveness in determining drug concentrations, mainly focusing on sibutramine quantification, a complex active pharmaceutical ingredient. The results indicate a strong correlation (R² = 0.987) between the two methodologies, with FTIR RMSE consistently yielding slightly higher results due to its sensitivity to molecular structural fluctuations and component interactions. In conclusion, this study advocates for integrating FTIR RMSE into pharmaceutical research practices. It emphasizes the need for calibration and refinement of this technique to further enhance estimation accuracy and analytical precision. It underscores the pivotal role of advanced analytical methods in various applications, including pharmaceutical and biomedical fields.

Machine-Learning- and Structure-Based Virtual Screening for Selecting Cinnamic Acid Derivatives as Leishmania major DHFR-TS Inhibitors.

The critical enzyme dihydrofolate reductase-thymidylate synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. Through consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in silico predictions were then validated through in vitro assays to examine the inhibitory capacity of the top-ranked naturally occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4'-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

Elucidating the microscopic origin of observed anti-correlation between the protein-protein and protein-water interaction energies

Water as a solvent plays an important role in dictating the structure and dynamics of the large biomolecules like proteins. It has been proposed that the protein dynamics and energetics are closely coupled to the water molecules in the hydration shell. In particular, it has been shown earlier that the fluctuations in intra-protein (protein-protein) interaction energy is strongly anti-correlated with the protein-water interaction energy (solvation energy). Moreover, the dynamical signatures of water gets reflected into the protein dynamics in terms of a dominant power law behavior. In this work, we have carried out systematic molecular dynamics (MD) simulations of three different protein systems to understand the key physical factors that contribute to such anti-correlations. First, we compare the dynamics in globular folded proteins like Lysozyme with intrinsically disordered peptides (IDPs) like Amyloid beta to show that enhanced conformational fluctuations lead to significantly stronger anti-correlation. Trp-cage miniprotein shows a similar behavior distributed over two sub-ensembles of folded and unfolded states. We also investigate what type of interactions and molecular processes are responsible for the observed anti-correlation. In particular, we observe that the extent of correlation decreases significantly in the order of charged, polar and non-polar amino acid residues. Charged residues that form salt bridge interactions show a dominant anti-correlation. Surprisingly, a few non-polar (hydrophobic and buried) residues demonstrate significant anti-correlation as well. We attribute this to the structural fluctuations that lead to an equilibrium between buried and solvent exposed states of these residues, where the protein-protein and protein-water interactions compensate each other. Our studies indicate that the molecular origin of the observed anti-correlation can be vary depending on the type of the interaction. The overall coupling/correlation is dominated by the electrostatic interactions and charged residues due to a general dielectric screening effect, whereas a few buried hydrophobic residues may also show such coupling due to structural dynamics between buried and exposed states.

Protein stability in a natural deep eutectic solvent: Preferential hydration or solvent slaving?

Deep eutectic solvents (DESs) emerged as potential alternative solvent media in multiple areas, including biomolecular (cryo)preservation. Herein, we studied the stability of a small protein (ubiquitin) in water and a betaine-glycerol-water (B:G:W) (1:2:ζ; ζ = 0, 1, 2, 5, 10) DES, through molecular dynamics. An AMBER-based model that accurately describes the density and shear viscosity of the DES is proposed. We find that water molecules are largely trapped in the solvent, precluding the formation of a full hydration layer, seemingly opposite to osmolytes’ preferential exclusion/preferential hydration mechanism. Although the protein is stable in the DES, structural fluctuations are largely suppressed and only recovered upon sufficient hydration. This is explained by a solvent-slaving mechanism where β-fluctuations are key, with the non-monotonic hydration of some amino acids with the water content providing an explanation to the non-monotonic folding of some proteins in aqueous DESs. A major thermal stability enhancement in the DES is also observed, caused by a similar slowdown of the backbone torsional dynamics. Our results support a kinetic stabilization of the protein in the DES, whereas a possible thermodynamic stabilization does not follow a preferential hydration or water entrapment mechanism.

Synthetic turbulence modelling for offshore wind farm engineering models using coherence aggregation

AbstractTurbulent wind fields are known to be a major driver for structural loads and power fluctuations on offshore wind turbines. At the single‐turbine scale, there exist well‐established design standards based on wind spectra and coherence functions calibrated from years of measurements, which are used to generate multiple 10‐min wind field realisations known as synthetic turbulence boxes, themselves used as input to turbine‐scale aero‐hydro‐servo elastic codes. These methods are however not directly applicable at farm scale. When analysing the dynamics of large offshore wind farms, measurements reveal the importance of large, low‐frequency turbulent vortices for power fluctuations and hence for wind farm control and grid integration. Also, farm‐scale wind fields are needed as input to farm‐scale aero‐servo‐elastic codes for the modelling of wake dynamics, affecting structural loads. These new concerns motivate an upgrade in the original turbine‐scale wind field representation: (1) spectral models need to be based on farm‐scale measurements, (2) the frozen‐turbulence assumption merging temporal and along‐wind coherence must be lifted, (3) simplifications are needed to reduce the number of degrees of freedom as the domain becomes excessively large. This paper suggests models and algorithms for aggregated farm‐wide corrrelated synthetic turbulence generation—lumping the wind field into space‐averaged quantities—adapted to the aero‐hydro‐servo elastic modelling of large offshore wind farms. Starting from the work of Sørensen et al. in the early 2000s for grid integration purposes, methods for structural load modelling (through wake meandering and high‐resolution wind field reconstruction) are introduced. Implementation and efficiency matters involving mathematical subtleties are then presented. Finally, numerical experiments are carried out to (1) verify the approach and implementation against a state‐of‐the‐art point‐based—as opposite to aggregated—synthetic turbulence generation code and (2) illustrate the benefit of turbulence aggregation for the modelling of large offshore wind farms.

Permeant cations modulate pore dynamics and gating of TRPV1 ion channels.

The transient receptor vanilloid 1 (TRPV1) is a non-selective ion channel, which is activated by several chemical ligands and heat. We have previously shown that activation of TRPV1 by different ligands results in single-channel openings with different conductance, suggesting that the selectivity filter is highly dynamic. TRPV1 is weakly voltage dependent; here, we sought to explore whether the permeation of different monovalent ions could influence the voltage dependence of this ion channel. By using single-channel recordings, we show that TRPV1 channels undergo rapid transitions to closed states that are directly connected to the open state, which may result from structural fluctuations of their selectivity filter. Moreover, we demonstrate that the rates of these transitions are influenced by the permeant ion, suggesting that ion permeation regulates the voltage dependence of these channels. Our data could be the basis for more detailed MD simulations exploring the permeation mechanism and how the occupancy of different ions alters the three-dimensional structure of the pore of TRPV1 channels.

Enlightenment of calcite veins in deep Ordovician Wufeng–Silurian Longmaxi shales fractures to migration and enrichment of shale gas in southern Sichuan Basin, SW China

The relationship between fracture calcite veins and shale gas enrichment in the deep Ordovician Wufeng Formation–Silurian Longmaxi Formation (Wufeng–Longmaxi) shales in southern Sichuan Basin was investigated through core and thin section observations, cathodoluminescence analysis, isotopic geochemistry analysis, fluid inclusion testing, and basin simulation. Tectonic fracture calcite veins mainly in the undulating part of the structure and non-tectonic fracture calcite veins are mainly formed in the gentle part of the structure. The latter, mainly induced by hydrocarbon generation, occurred at the stage of peak oil and gas generation, while the former turned up with the formation of Luzhou paleouplift during the Indosinian. Under the influence of hydrocarbon generation pressurization process, fractures were opened and closed frequently, and oil and gas episodic activities are recorded by veins. The formation pressure coefficient at the maximum paleodepth exceeds 2.0. The formation uplift stage after the Late Yanshanian is the key period for shale gas migration. Shale gas migrates along the bedding to the high part of the structure. The greater the structural fluctuation is, the more intense the shale gas migration activity is, and the loss is more. The gentler the formation is, the weaker the shale gas migration activity is, and the loss is less. The shale gas enrichment in the core of gentle anticlines and gentle synclines is relatively higher.

Solvent Effects and pH Dependence of the X-ray Absorption Spectra of Proline from Electrostatic Embedding Quantum Mechanics/Molecular Mechanics and Mixed-Reference Spin-Flip Time-dependent Density-Functional Theory.

The accurate description of solvent effects on X-ray absorption spectra (XAS) is fundamental for comparing the simulated spectra with experiments in solution. Currently, few protocols exist that can efficiently reproduce the effects of the solute/solvent interactions on XAS. Here, we develop an efficient and accurate theoretical protocol for simulating the solvent effects on XAS. The protocol combines electrostatic embedding QM/MM based on electrostatic potential fitted operators for describing the solute/solvent interactions and mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT) for simulating accurate XAS spectra. To demonstrate the capabilities of our protocol, we compute the X-ray absorption of neutral proline in the gas phase and ionic proline in water in all relevant K-edges, showing excellent agreement with experiments. We show that states represented by core to π* transitions are almost unaffected by the interaction with water, whereas the core to σ* transitions are more impacted by the fluctuation of proline structure and the electrostatic interaction with the solvent. Finally, we reconstruct the pH-dependent XAS of proline in solution, determining that the N K-edge can be used to distinguish its three protonation states.

Exceptional points in periodic array of silicon rods

We find numerically the complex eigenvalues in grating composed of infinitely long silicon rods of rectangular cross section and show existence of exceptional points (EPs) in parametric space of structural scales and wave vector along the rods. The EPs have sufficiently small imaginary parts due to their proximity to bound states in the continuum. This enables to trace the resonant frequencies in the transmission around the EP and, accordingly, to identify the EP by bifurcation of the transmission. We present generic coupled mode theory to elucidate this effect. We also show that structural fluctuations of grating preserve EP but obscures their observation because of inhomogeneous broadening of transmission peaks.

Dynamics of mitochondrial membranes under photo-oxidative stress with high spatiotemporal resolution.

In our study, we harnessed an original Enhanced Speed Structured Illumination Microscopy (Fast-SIM) imaging setup to explore the dynamics of mitochondrial and inner membrane ultrastructure under specific photo-oxidation stress induced by Chlorin-e6 and light irradiation. Notably, our Fast-SIM system allowed us to observe and quantify a distinct remodeling and shortening of the mitochondrial structure after 60-80s of irradiation. These changes were accompanied by fusion events of adjacent inner membrane cristae and global swelling of the organelle. Preceding these alterations, a larger sequence was characterized by heightened dynamics within the mitochondrial network, featuring events such as mitochondrial fission, rapid formation of tubular prolongations, and fluctuations in cristae structure. Our findings provide compelling evidence that, among enhanced-resolution microscopy techniques, Fast-SIM emerges as the most suitable approach for non-invasive dynamic studies of mitochondrial structure in living cells. For the first time, this approach allows quantitative and qualitative characterization of successive steps in the photo-induced oxidation process with sufficient spatial and temporal resolution.

Fully exposed (101) plane endowing CoSe anode with fast and stable potassium storage

Transition-metal selenides, especially cobalt selenides (CoSe), are widely regarded as a promising anode for potassium-ion batteries (KIBs) due to their high theoretical capacity and good electrical conductivity. However, CoSe easily suffers from a substantial volume change upon repeated cycling, leading to a fast capacity decay and poor cycling stability. Herein, a dual-carbon confined CoSe is successfully designed by using metal-organic frameworks as raw materials. Various characterizations disclose that the introduction of the extra carbon phase is conducive to the growth of (101) plane of CoSe, and based on this, rationally regulating carbonization temperature can further promote the exposure of (101) plane. Such fully exposed (101) plane not only provides sufficient active surface to uptake K-ions, but also favors the accommodation of electrode structure fluctuation, accounting for a high capacity and prolonged cycle lifespan. As a result, the optimized sample (denoted as 750 °CNC@CoSe/NC) delivers 392.5 mAh g−1 at 0.5 A g−1, accompanied by an excellent cycling stability over 400 cycles with 196.7 mAh g−1 at a high current density of 1 A g−1. This work is expected to offer effective guidance for constructing advanced CoSe anode toward KIBs.

Strong atom capture ability and pinning effect by doping an element with large electronegativity difference in Sb2Te3 phase change material

The ultimate goal of memory researchers and developers is to devise a universal memory to replace all memories in complex hierarchies of memory systems. Phase change memory is considered by the International Semiconductor Industry Association as the most likely emerging storage technology to achieve this ambitious goal due to its excellent performance. However, the relatively slow operation speed and poor cycle endurance are stumbling blocks for this purpose. Here, we propose a new doping strategy to construct stable bonding by introducing atoms with large electronegativity differences from the matrix Te atoms enhancing the capture ability and the pinning effect to Te atoms, which facilitates fast nucleation and suppresses migration of Te atoms to achieve significant performance improvement. Using ab initio molecular dynamics simulations, we explore and compare the atomic structures, chemical bonding, and dynamics properties of Hf doped Sb2Te3 (HfST), La doped Sb2Te3 (LaST), Rb doped Sb2Te3 (RbST) and Sr doped Sb2Te3 (SrST). In the XST (X refers to Hf, Rb, La and Sr atoms) systems, the increase of the more stable ring structure fluctuation and the stronger atom capture capability of rings enable more and faster formation of nuclei during crystallization. Higher Peierls-like distortions suggest better thermal stability. The motility of Te atoms is suppressed due to the pinning effect. High coordination of atoms and the concentration reduction of the lone-pair electron and void enable small density difference. Our results show that fast universal memory with good endurance can be achieved by the construction of strong bonding by doping atoms with large electronegativity differences, providing an important guidance for experiments and industries.

Structural Fluctuation, Relaxation, and Folding of Protein: An Approach Based on the Combined Generalized Langevin and RISM/3D-RISM Theories

In 2012, Kim and Hirata derived two generalized Langevin equations (GLEs) for a biomolecule in water, one for the structural fluctuation of the biomolecule and the other for the density fluctuation of water, by projecting all the mechanical variables in phase space onto the two dynamic variables: the structural fluctuation defined by the displacement of atoms from their equilibrium positions, and the solvent density fluctuation. The equation has an expression similar to the classical Langevin equation (CLE) for a harmonic oscillator, possessing terms corresponding to the restoring force proportional to the structural fluctuation, as well as the frictional and random forces. However, there is a distinct difference between the two expressions that touches on the essential physics of the structural fluctuation, that is, the force constant, or Hessian, in the restoring force. In the CLE, this is given by the second derivative of the potential energy among atoms in a protein. So, the quadratic nature or the harmonicity is only valid at the minimum of the potential surface. On the contrary, the linearity of the restoring force in the GLE originates from the projection of the water’s degrees of freedom onto the protein’s degrees of freedom. Taking this into consideration, Kim and Hirata proposed an ansatz for the Hessian matrix. The ansatz is used to equate the Hessian matrix with the second derivative of the free-energy surface or the potential of the mean force of a protein in water, defined by the sum of the potential energy among atoms in a protein and the solvation free energy. Since the free energy can be calculated from the molecular mechanics and the RISM/3D-RISM theory, one can perform an analysis similar to the normal mode analysis (NMA) just by diagonalizing the Hessian matrix of the free energy. This method is referred to as the Generalized Langevin Mode Analysis (GLMA). This theory may be realized to explore a variety of biophysical processes, including protein folding, spectroscopy, and chemical reactions. The present article is devoted to reviewing the development of this theory, and to providing perspective in exploring life phenomena.

Beyond spreading rate: Controls on the thermal regime of mid-ocean ridges.

The thermal state of mid-ocean ridges exerts a crucial modulation on seafloor spreading processes that shape ~2/3 of our planet's surface. Standard thermal models treat the ridge axis as a steady-state boundary layer between the hydrosphere and asthenosphere, whose thermal structure primarily reflects the local spreading rate. This framework explains the deepening of axial melt lenses (AMLs)-a proxy for the basaltic solidus isotherm-from ~1 to ~3 km from fast- to intermediate-spreading ridges but fails to account for shallow crustal AMLs documented at slow-ultraslow spreading ridges. Here, we show that these can be explained by a numerical model that decouples the potentially transient ridge magma supply from spreading rate, captures the essential physics of hydrothermal convection, and considers multiple modes of melt emplacement. Our simulations show that melt flux is a better thermal predictor than spreading rate. While multiple combinations of melt/dike emplacement modes, permeability structure, and temporal fluctuations of melt supply can explain shallow crustal AMLs at slow-ultraslow ridges, they all require elevated melt fluxes compared to most ridge sections of comparable spreading rates. This highlights the importance of along-axis melt focusing at slow-ultraslow ridges and sheds light on the natural variability of their thermal regimes.

Crystal structures of QseE and QseG: elements of a three-component system from Escherichia coli.

Bacteria regulate virulence by using two-component systems (TCSs) composed of a histidine kinase (HK) and a response regulator (RR). TCSs respond to environmental signals and change gene-expression levels. The HK QseE and the RR QseF regulate the virulence of Enterobacteriaceae bacteria such as enterohemorrhagic Escherichia coli. The operon encoding QseE/QseF also contains a gene encoding an outer membrane lipoprotein, qseG. The protein product QseG interacts with QseE in the periplasmic space to control the activity of QseE and constitutes a unique QseE/F/G three-component system. However, the structural bases of their functions are unknown. Here, crystal structures of the periplasmic regions of QseE and QseG were determined with the help of AlphaFold models. The periplasmic region of QseE has a helix-bundle structure as found in some HKs. The QseG structure is composed of an N-terminal globular domain and a long C-terminal helix forming a coiled-coil-like structure that contributes to dimerization. Comparison of QseG structures obtained from several crystallization conditions shows that QseG has structural polymorphisms at the C-terminus of the coiled-coil structure, indicating that the C-terminus is flexible. The C-terminal flexibility is derived from conserved hydrophilic residues that reduce the hydrophobic interaction at the coiled-coil interface. Electrostatic surface analysis suggests that the C-terminal coiled-coil region can interact with QseE. The observed structural fluctuation of the C-terminus of QseG is probably important for interaction with QseE.

A Highly Ordered Nitroxide Side Chain for Distance Mapping and Monitoring Slow Structural Fluctuations in Proteins.

The online version contains supplementary material available at 10.1007/s00723-023-01618-8.