Unseen Mode Research Articles

The crystal structure of Nictaba reveals its carbohydrate-binding properties and a new lectin dimerization mode.

Nictaba is a (GlcNAc)n-binding, stress-inducible lectin from Nicotiana tabacum that serves as a representative for the Nictaba-related lectins, a group of proteins that play pivotal roles in plant defense mechanisms and stress response pathways. Despite extensive research into biological activities and physiological role(s) of the lectin, the three-dimensional structure of Nictaba remained largely unknown. Here, we report crystal structures for Nictaba in the apo form and bound to chitotriose. The structures reveal that the Nictaba protomer has a jelly-roll fold, similar to the cucumber lectin Cus17, but exhibit a unique and previously unseen mode of dimerization. The chitotriose binding mode, similar to Cus17, centers around the central GlcNAc residue, providing insights into the determinants of specificity of Nictaba towards carbohydrate structures. By integrating these structural insights with inputs from glycan arrays, molecular docking, and molecular dynamics simulations, we propose that Nictaba employs a single carbohydrate-recognition domain within each of the two subunits in the dimer to display pronounced specificity towards GlcNAc-containing carbohydrates. Furthermore, we identified amino acid residues involved in the extended binding site capable of accommodating structurally diverse high-mannose and complex N-glycans. Glycan array and in silico analyses revealed interactions centered around the conserved Man3GlcNAc2 core, explaining the broad recognition of N-glycan structures. Collectively, the structural and biochemical insights presented here fill a void into the atlas of lectin structure-function relationships and pave the way for future developments in plant stress biology and lectin-based applications.

Weighted Conditional Discriminant Analysis for Unseen Operating Modes Fault Diagnosis in Chemical Processes

One challenge faced by data-driven fault diagnosis methods is that they may perform well over the operating modes where the historical data are collected, but fail to generalize to unseen modes that have never appeared before. That is one of the root causes that have prevented many advanced fault diagnosis methods from being widely accepted by the chemical industry. Consequently, it is significant to develop a novel fault diagnosis method, which can build a model to determine the type of faults occurred on unseen modes. On the other hand, one chemical process generally experiences multiple operating modes, from which common knowledge of these modes can be extracted and be applied to an unseen mode. To this end, a novel weighted conditional discriminant analysis (WCDA) algorithm is proposed by adopting the context of domain generalization (DG) approaches to leverage and distill the knowledge from historical modes for unseen modes of fault diagnosis. Specifically, a novel variable weighting scheme is developed based on the Kullback–Leibler divergence between features of different modes. Then, a fault diagnosis model is constructed by learning a classifier and invariant feature representation simultaneously. Moreover, WCDA is extended to the context of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">domain adaptation</i> (DA), where the performance of the fault diagnosis model is further improved by leveraging the unlabeled data collected from a new mode. Empirical results on a numerical example, the Tennessee Eastman process, and continuous stirred tank chemical reactor demonstrate the effectiveness of our method.

Record Alkali Metal Intercalation by Highly Charged Corannulene.

The need for advanced energy storage technologies demands the development of new functional materials. Novel carbon-rich and carbon-based materials of different structural topologies attract significant attention in this regard. Attractive systems include a unique class of bowl-shaped polycyclic aromatic hydrocarbons that map onto fullerene surfaces and are thus often referred to as fullerene fragments, buckybowls, or π-bowls. Importantly, carbon bowls are able to acquire multiple electrons in stepwise reduction reactions producing sets of successively reduced carbanions. The resulting negatively charged π-bowls exhibit unique supramolecular assembly and metal intercalation patterns that only recently have begun to be uncovered. First, we have resolved the long-standing mystery behind the supramolecular structure formed by a highly reduced fullerene fragment called corannulene (C20H104-) with multiple lithium ions, using X-ray crystallography coupled with NMR spectroscopy and theoretical calculations. This work provided a new paradigm for lithium ion intercalation between the curved carbon π-surfaces and facilitated understanding of the lithium ion storage mechanism in carbonaceous matrices. Next, we have initiated a new research direction, an investigation of the mixed alkali metal reduction reactions using bowl-shaped corannulene as a remarkable multielectron reservoir and unique ligand with open convex and concave π-surfaces. As a result, we have revealed the cooperative effect of lithium with heavier Group 1 metals in reduction and self-assembly processes of corannulene. Moreover, we have discovered a new class of organometallic supramolecules having heterometallic cores with high nuclearity and charge such as Li3M36+ and LiM56+ (M = K, Rb, and Cs) sandwiched between two tetrareduced corannulene decks. The resulting triple-decker supramolecular assemblies, fully characterized by X-ray diffraction and spectroscopic methods, were found to exhibit a record ability of the highly charged corannulene π-surfaces to be fully engaged in intercalation of multiple metal ions. Based on this unique ability, curved π-ligands with extended carbon frameworks are expected to show remarkable potential for alkali metal storage compared to flat polycyclic arenes. Notably, a previously unseen mode of internal lithium binding revealed in the heterobimetallic sandwiches is accompanied by unprecedented negative shifts (up to -25 ppm) in 7Li NMR spectra. Based on in-depth analysis of NMR data, augmented by DFT calculations, we have rationalized the observed experimental trends and proposed the mechanism of stepwise alkali metal substitution reactions. Furthermore, we have correlated the origin of the record 7Li NMR shifts with unique electronic structures of these novel supramolecular aggregates. Herein we present comprehensive analysis of unusual structural and electronic features of remarkable heterometallic self-assemblies formed by tetrareduced corannulene, using a wealth of our recent experimental and computational results. This work uncovers unique potential of highly negatively charged bowl-shaped π-ligands for new supramolecular chemistry and materials chemistry applications.

Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis.

Mycobacteria are characterized by their impermeable outer membrane, which is rich in mycolic acids1. To transport substrates across this complex cell envelope, mycobacteria rely on type VII (also known as ESX) secretion systems2. In Mycobacterium tuberculosis, these ESX systems are essential for growth and full virulence and therefore represent an attractive target for anti-tuberculosis drugs3. However, the molecular details underlying type VII secretion are largely unknown, due to a lack of structural information. Here, we report the molecular architecture of the ESX-5 membrane complex from Mycobacterium xenopi determined at 13 Å resolution by electron microscopy. The four core proteins of the ESX-5 complex (EccB5, EccC5, EccD5 and EccE5) assemble with equimolar stoichiometry into an oligomeric assembly that displays six-fold symmetry. This membrane-associated complex seems to be embedded exclusively in the inner membrane, which indicates that additional components are required to translocate substrates across the mycobacterial outer membrane. Furthermore, the extended cytosolic domains of the EccC ATPase, which interact with secretion effectors, are highly flexible, suggesting an as yet unseen mode of substrate interaction. Comparison of our results with known structures of other bacterial secretion systems demonstrates that the architecture of type VII secretion system is fundamentally different, suggesting an alternative secretion mechanism.

Structural Insights into Nonspecific Binding of DNA by TrmBL2, an Archaeal Chromatin Protein

The crystal structure of TrmBL2 from the archaeon Pyrococcus furiosus shows an association of two pseudosymmetric dimers. The dimers follow the prototypical design of known bacterial repressors with two helix–turn–helix (HTH) domains binding to successive major grooves of the DNA. However, in TrmBL2, the two dimers are arranged at a mutual displacement of approximately 2bp so that they associate with the DNA along the double-helical axis at an angle of approximately 80°.While the deoxyribose phosphate groups of the double-stranded DNA (dsDNA) used for co-crystallization are clearly seen in the electron density map, most of the nucleobases are averaged out. Refinement required to assume a superposition of at least three mutually displaced dsDNAs. The HTH domains interact primarily with the deoxyribose phosphate groups and polar interactions with the nucleobases are almost absent.This hitherto unseen mode of DNA binding by TrmBL2 seems to arise from nonoptimal protein–DNA contacts made by its four HTH domains resulting in a low-affinity, nonspecific binding to DNA.

Dynamically modeling fault step overs using various friction laws

AbstractIt is well known that fault step overs can under some circumstances allow through‐going rupture and under other circumstances cause rupture to terminate. However, the effects of different friction law formulations on jumping rupture have not been extensively explored. In this study we use the 2‐D dynamic finite element method to investigate how different frictional parameterizations affect the ability of rupture to jump a step over, in both extensional and compressional settings. We compare linear slip‐weakening friction and three forms of rate‐ and state‐dependent friction: the aging law, slip law, and slip law with strong rate weakening. We have found that for friction parameterizations with the same effective slip‐weakening distance, the functional forms of such friction laws can have a significant effect on maximum jump distance. With friction laws scaled to have equivalent fracture energies, we find that the functional forms of such friction laws have a second‐order effect on jumping rupture. Finally, with our specific parameterizations we find that delays in rupture across the step over systems can lead to a previously unseen mode of supershear transition once the rupture renucleates on the secondary fault segment, even if the initial stress field precludes such a transition. Studies using multiple friction laws in complex geometries such as fault step overs can lead to better understanding of the dependence of rupture properties on the type of friction law utilized in models and statistical analysis.

High-resolution crystal structure reveals molecular details of target recognition by bacitracin

Bacitracin is a metalloantibiotic agent that is widely used as a medicine and feed additive. It interferes with bacterial cell-wall biosynthesis by binding undecaprenyl-pyrophosphate, a lipid carrier that serves as a critical intermediate in cell wall production. Despite bacitracin's broad use, the molecular details of its target recognition have not been elucidated. Here we report a crystal structure for the ternary complex of bacitracin A, zinc, and a geranyl-pyrophosphate ligand at a resolution of 1.1 Å. The antibiotic forms a compact structure that completely envelopes the ligand's pyrophosphate group, together with flanking zinc and sodium ions. The complex adopts a highly amphipathic conformation that offers clues to antibiotic function in the context of bacterial membranes. Bacitracin's efficient sequestration of its target represents a previously unseen mode for the recognition of lipid pyrophosphates, and suggests new directions for the design of next-generation antimicrobial agents.

Mode characterisation inδScuti stars

We present new spectroscopic observations of four bright Scuti pulsators. Line indices of the Balmer lines can be used to establish mode identications using the ratio R between such line index amplitudes and photometric amplitudes. For the well known radial pulsator Pup an absolute value of the amplitude ratio of the radial mode was found to R =0 :43, consistent with earlier values of R 0:5 reported for other Scuti stars. In GN And we recover the recently reported newly excited mode, while the former dominant mode was not recovered. We conrm that V1208 Aql is a non-radial pulsator, containing two modes of dierent degree. In V1208 Aql we report a previously unseen mode behavior: the phases of both modes are reversed between the core and wings of the H line, suggesting the presence of more undetected modes. For AV Cet we nd that the dominant mode is a previously undetected one. We suggest the undertaking of new photometric observations of Pup, GN And, V1208 Aql and AV Cet to determine the frequencies and amplitudes of the pulsations.

Acoustic anomalies inTb2(MoO4)3and the "missing"A1optic mode

Anomalies in both the acoustic- and optic-phonon spectra associated with the ferroelectric and ferroelastic phase transition in terbium molybdate have been quantitatively measured by simultaneous Brillouin and Raman spectroscopy. The most striking singular behavior observed is the divergent damping of both the ${A}_{1}$ optic phonon and the ${C}_{11}$ acoustic phonon upon approach to ${T}_{0}$ from below. ${T}_{0}$ was determined to be 159\ifmmode^\circ\else\textdegree\fi{}C for our sample by measurement of the pyroelectric response. The ${A}_{1}$-mode frequency determined from the Raman spectrum shows little temperature dependence, while the ${C}_{11}$ elastic constant determined from the Brillouin spectra decreases by about 60% between room temperature and ${T}_{0}$. There is no evidence of a dynamic central peak. The observed anomalies in the acoustic velocity and damping are incompatible with a model based on bilinear coupling between the acoustic mode and the ${A}_{1}$ mode seen in the Raman spectrum. However, a satisfactory account of all the experimental observations (including the anomalies in ${\stackrel{\ifmmode \tilde{}\else \~{}\fi{}}{C}}_{11}$ and ${C}_{22}$) can be obtained by assuming the presence of a second ${A}_{1}$ optic phonon with a negligible Raman scattering cross section. We note that the dynamic variables below ${T}_{0}$ are not simply related to the distortion, as has often been assumed previously. On the basis of this model we use the acoustic velocities and damping to determine the frequency and damping parameters of this unseen mode. It is emphasized that the singular behavior of the damping of the observed ${A}_{1}$ mode has yet to receive adequate theoretical explanation.