Inherent Structural Flexibility Research Articles

Multistate structures in a hydrogen-bonded polycatenation non-covalent organic framework with diverse resistive switching behaviors

The inherent structural flexibility and reversibility of non-covalent organic frameworks have enabled them to exhibit switchable multistate structures under external stimuli, providing great potential in the field of resistive switching (RS), but not well explored yet. Herein, we report the 0D+1D hydrogen-bonded polycatenation non-covalent organic framework (HOF-FJU-52), exhibiting diverse and reversible RS behaviors with the high performance. Triggered by the external stimulus of electrical field E at room temperature, HOF-FJU-52 has excellent resistive random-access memory (RRAM) behaviors, comparable to the state-of-the-art materials. When cooling down below 200 K, it was transferred to write-once-read-many-times memory (WORM) behaviors. The two memory behaviors exhibit reversibility on a single crystal device through the temperature changes. The RS mechanism of this non-covalent organic framework has been deciphered at the atomic level by the detailed single-crystal X-ray diffraction analyses, demonstrating that the structural dual-flexibility both in the asymmetric hydrogen bonded dimers within the 0D loops and in the infinite π–π stacking column between the loops and chains contribute to reversible structure transformations between multi-states and thus to its dual RS behaviors.

Structural Flexibility of Tau in Its Interaction with Microtubules as Viewed by Site-Directed Spin Labeling EPR Spectroscopy.

Tau is a microtubule-associated protein that belongs to the Intrinsically Disordered Proteins (IDPs) family. IDPs or Intrinsically Disordered Regions (IDRs) play key roles in protein interaction networks and their dysfunctions are often related to severe diseases. Defined by their lack of stable secondary and tertiary structures in physiological conditions while being functional, these proteins use their inherent structural flexibility to adapt to and interact with various binding partners. Knowledges on the structural dynamics of IDPs and their different conformers are crucial to finely decipher fundamental biological processes controlled by mechanisms such as conformational adaptations or switches, induced fit, or conformational selection events. Different mechanisms of binding have been proposed: among them, the so-called folding-upon-binding in which the IDP adopts a certain conformation upon interacting with a partner protein, or the formation of a "fuzzy" complex in which the IDP partly keeps its dynamical character at the surface of its partner. The dynamical nature and physicochemical properties of unbound as well as bound IDPs make this class of proteins particularly difficult to characterize by classical bio-structural techniques and require specific approaches for the fine description of their inherent dynamics.Among other techniques, Site-Directed Spin Labeling combined with Electron Paramagnetic Resonance (SDSL-EPR) spectroscopy has gained much interest in this last decade for the study of IDPs. SDSL-EPR consists in grafting a paramagnetic label (mainly a nitroxide radical) at selected site(s) of the macromolecule under interest followed by its observation using and/or combining different EPR strategies. These nitroxide spin labels detected by continuous wave (cw) EPR spectroscopy are used as perfect reporters or "spy spins" of their local environment, being able to reveal structural transitions, folding/unfolding events, etc. Another approach is based on the measurement of inter-label distance distributions in the 1.5-8.0nm range using pulsed dipolar EPR experiments, such as Double Electron-Electron Resonance (DEER) spectroscopy. The technique is then particularly well suited to study the behavior of Tau in its interaction with its physiological partner: microtubules (MTs). In this chapter we provide a detailed experimental protocol for the labeling of Tau protein and its EPR study while interacting with preformed (Paclitaxel-stabilized) MTs, or using Tau as MT inducer. We show how the choice of nitroxide label can be crucial to obtain functional information on Tau/tubulin complexes.

De Novo Single-Stranded RNA-Binding Peptides Discovered by Codon-Restricted mRNA Display.

RNA-binding proteins participate in diverse cellular processes, including DNA repair, post-transcriptional modification, and cancer progression through their interactions with RNAs, making them attractive for biotechnological applications. While nature provides an array of naturally occurring RNA-binding proteins, developing de novo RNA-binding peptides remains challenging. In particular, tailoring peptides to target single-stranded RNA with low complexity is difficult due to the inherent structural flexibility of RNA molecules. Here, we developed a codon-restricted mRNA display and identified multiple de novo peptides from a peptide library that bind to poly(C) and poly(A) RNA with KDs ranging from micromolar to submicromolar concentrations. One of the newly identified peptides is capable of binding to the cytosine-rich sequences of the oncogenic Cdk6 3'UTR RNA and MYU lncRNA, with affinity comparable to that of the endogenous binding protein. Hence, we present a novel platform for discovering de novo single-stranded RNA-binding peptides that offer promising avenues for regulating RNA functions.

Iridium complexes of acridine-based PNP-type pincer ligands: Synthesis, structure and reactivity

Acridine-based PNP-type pincer ligands (AcrPNP) have previously been used for the construction of a small number of Ru(II), Mn(I), Rh(III) and Ir(III) complexes, with most attention being given to the catalytically-active ruthenium complexes. In the present work, we significantly expand the scope of known AcrPNP complexes by introducing a series of new Ir(I) and Ir(III) complexes. These were synthesized from two AcrPNP ligands differing in their P-substituents (iPr vs Ph), in conjunction with various Ir(I)-olefin precursors, through different sequences of reactions that include intramolecular CH activations and additions of H2 and NaBEt3H. The new iridium complexes, with their observed structures and reactivities, reflect the unique properties of the acridine-based PNP ligands, i.e., their inherent structural flexibility and ability to support both metal-centered reactivity (CH and HH oxidative addition) and ligand-centered reactivity (hydride- and H2-induced dearomatization).

Negative Thermal Expansion in the Noncarboxylate Based Metal–Organic Framework Cd(trz)Cl

Negative thermal expansion (NTE), as a counterintuitive phenomenon, has attracted considerable interest owing to its great scientific and technical value. Owing to the inherent structural flexibility, metal–organic frameworks (MOFs) have recently been recognized as an ideal platform for the study of NTE. However, the reported NTE MOFs are mainly restrained in the carboxylate based ones. Herein, we found that the noncarboxylate MOF Cd(trz)Cl (trz = 1,2,4-trizaole) can also exhibit intrinsic volumetric NTE, and a transition from NTE to PTE at high temperatures can be observed. The combined in situ synchrotron powder X-ray diffraction, Raman spectra measurements, and DFT calculations shed light on the fact that the NTE mainly originates from the synergistic effect of geometric flexibility and the enhanced out-of-plane rotation behavior of the trz ligand. This study not only demonstrates a new NTE material but also can help to extend the scope of NTE to the more diverse noncarboxylate based MOFs.

Mapping the conformational energy landscape of Abl kinase using ClyA nanopore tweezers

Protein kinases play central roles in cellular regulation by catalyzing the phosphorylation of target proteins. Kinases have inherent structural flexibility allowing them to switch between active and inactive states. Quantitative characterization of kinase conformational dynamics is challenging. Here, we use nanopore tweezers to assess the conformational dynamics of Abl kinase domain, which is shown to interconvert between two major conformational states where one conformation comprises three sub-states. Analysis of kinase-substrate and kinase-inhibitor interactions uncovers the functional roles of relevant states and enables the elucidation of the mechanism underlying the catalytic deficiency of an inactive Abl mutant G321V. Furthermore, we obtain the energy landscape of Abl kinase by quantifying the population and transition rates of the conformational states. These results extend the view on the dynamic nature of Abl kinase and suggest nanopore tweezers can be used as an efficient tool for other members of the human kinome.

Modeling and Contouring Control for Cantilever Beam Machine With Structural Flexibility

In biaxial contouring control applications, the inherent structural flexibility of machines can lead to position discrepancies between the manipulator and actuator, and thus deteriorate the manufacturing performance, especially when the controller is designed without available end-effector side feedback. In this work, we focus on the end-effector contouring control problem for industrial machines with position-dependent flexibility to improve the contouring performance while eliminating the effect of mechanical vibration. A model for the widely used cantilever beam machine is developed to describe the dynamics of the end-effector by capturing the rotation and coupled dynamics between axes. The proposed model is validated through experiment and systematically reduced to switched linear time-invariant models for controller design. By adopting the extended state observer, the proposed control architecture decouples the dynamics between the X and Y-axis and simplifies the controller design process. The model predictive control method is utilised for improving the contouring performance while reducing mechanical vibration. The efficacy of the proposed control framework is demonstrated and validated on the designed high-fidelity model. Performance comparisons between the proposed approach with benchmark controllers are presented.

Prevalence and functionality of intrinsic disorder in human FG-nucleoporins

The nuclear-cytoplasmic transport of biomolecules is assisted by the nuclear pores composed of evolutionarily conserved proteins termed nucleoporins (Nups). The central Nups, characterized by multiple FG-repeats, are highly dynamic and contain a high level of intrinsically disordered regions (IDPRs). FG-Nups bind several protein partners and play critical roles in molecular interactions and the regulation of cellular functions through their IDPRs. In the present study, we performed a multiparametric bioinformatics analysis to characterize the prevalence and functionality of IDPRs in human FG-Nups. These analyses revealed that the sequence of all FG-Nups contained >50% IDPRs (except Nup54 and Nup358). Nup98, Nup153, and POM121 were extremely disordered with ~80% IDPRs. The functional disorder-based binding regions in the FG-Nups were identified. The phase separation behavior of FG-Nups indicated that all FG-Nups have the potential to undergo liquid-to-liquid phase separation that could stabilize their liquid state. The inherent structural flexibility in FG-Nups is mechanistically and functionally advantageous. Since certain FG-Nups interact with disease-relevant protein aggregates, their complexes can be exploited for drug design. Furthermore, consideration of the FG-Nups from the intrinsic disorder perspective provides critical information that can guide future experimental studies to uncover novel pathways associated with diseases linked with protein misfolding and aggregation.

Polar Metal Phase Induced by Oxygen Octahedral Network Relaxation in Oxide Thin Films

ABO3 perovskite materials and their derivatives have inherent structural flexibility due to the corner sharing network of the BO6 octahedron, and the large variety of possible structural distortions and strong coupling between lattice and charge/spin degrees of freedom have led to the emergence of intriguing properties, such as high-temperature superconductivity, colossal magnetoresistance, and improper ferroelectricity. Here, an unprecedented polar ferromagnetic metal phase in SrRuO3 (SRO) thin films is presented, arising from the strain-controlled oxygen octahedral rotation (OOR) pattern. For compressively strained SRO films grown on SrTiO3 substrate, oxygen octahedral network relaxation is accompanied by structural phase separation into strained tetragonal and bulk-like orthorhombic phases, and the asymmetric OOR evolution across the phase boundary allows formation of the polar phase, while bulk metallic and ferromagnetic properties are maintained. From the results, it is expected that other oxide perovskite thin films will also yield similar structural environments with variation of OOR patterns, and thereby provide promising opportunities for atomic scale control of material properties through strain engineering.

Front Cover: Luminescent Coordination Polymers Constructed from a Flexible, Tetradentate Diisopyrazole Ligand and Copper(I) Halides (Chem. Asian J. 5/2020)

An ethylene-bridged diisopyrazole ligand forms one- and two-dimensional luminescent coordination polymers through complexation with Cu(I) halides. While chloride and bromide form infinite coordination chains with trigonal planar copper(I) coordination geometry, iodide results in the formation of a coordination network with stair-step type Cu4I4 subunits that exhibits thermochromic emission. These results illustrate the inherent structural flexibility of the diisopyrazole ligand to adopt both planar and stepped conformations in the solid state. More information can be found in the Full Paper by Yasuhide Inokuma et al. on page 601 in Issue 5, 2020 (DOI: 10.1002/asia.201901682).

Triple‐mode bandpass filter

triple‐mode bandpass filter

Non-conventional synthesis and photophysical studies of platinum(ii) complexes with methylene bridged 2,2'-dipyridylamine derivatives.

Methylene bridged 2,2'-dipyridylamine (dpa) derivatives and their metal complexes possess outstanding properties due to their inherent structural flexibility. Synthesis of such complexes typically involves derivatization of dpa followed by coordination on metals, and may not always be very efficient. In this work, an alternative synthetic approach, involving the derivatization step after - rather than prior to - coordination of dpa on metal center, is proposed and applied to synthesis of a number of platinum(ii) complexes with substituted benzyldi(2-pyridyl)amines. Comparison with the more conventional synthetic route reveals greater efficiency and versatility of the proposed approach. The obtained complexes are not luminescent in solution at room temperature, but display blue phosphorescence emission (ca. 415 nm) with the lifetimes of μs order in glassy matrix at 77 K, with additional green (ca. 485 nm) and relatively long living (τ = 3.7 ms) emission in the case of iodine substituted derivative.

Multiple claudin\u2013claudin cis interfaces are required for tight junction strand formation and inherent flexibility

Tight junctions consist of a network of sealing strands that create selective ion permeability barriers between adjoining epithelial or endothelial cells. The current model for tight junction strands consists of paired rows of claudins (Cldn) coupled by a cis interface (X-1) derived from crystalline Cldn15. Here we show that tight junction strands exhibit a broad range of lateral bending, indicating diversity in cis interactions. By combining protein–protein docking, coevolutionary analysis, molecular dynamics, and a mutagenesis screen, we identify a new Cldn–Cldn cis interface (Cis-1) that shares interacting residues with X-1 but has an ~ 17° lateral rotation between monomers. In addition, we found that a missense mutation in a Cldn14 that causes deafness and contributes stronger to Cis-1 than to X-1 prevents strand formation in cultured cells. Our results suggest that Cis-1 contributes to the inherent structural flexibility of tight junction strands and is required for maintaining permeability barrier function and hearing.

Engineering Isoreticular 2D Metal–Organic Frameworks with Inherent Structural Flexibility

The chemical mutability of metal–organic frameworks (MOFs) is an advantageous feature that allows fine-tuning of their physical and chemical properties. Herein, we report the successful isoreticulation of a MOF with an outstanding gas selectivity for CO2 versus N2: [Cu(L1)(H2O)]·xS (CuL1), where H2L1 = bis(4-(4-carboxyphenyl)-1H-pyrazolyl)methane) and S = solvate. By modifying the steric bulk and length of the original ligand, we synthesised three new MOFs with 2D networks isoreticular to CuL1, namely [Cu(L1Me)(H2O)]·xS (CuL1Me), [Cu(L2)(H2O)]·xS (CuL2), and [Cu(L2Me)(H2O)]·xS (CuL2Me) (where H2L1Me = bis(4-(4-carboxyphenyl)-3,5-dimethyl-1H-pyrazolyl)methane, H2L2 = bis(4-(4-carboxyphenyl)-(ethyne-2,1-yl)-1H-pyrazolyl)methane, and H2L2Me = bis(4-(4-carboxyphenyl)-(ethyne-2,1-yl)-3,5-dimethyl-1H-pyrazolyl)methane). Depending on the steric hindrance and structure metrics of the organic links, staggered and eclipsed arrangements of 2D 44 net layers were obtained. The anisotropy of the pore dimensions is proportional to the linker length (L2 and L2Me), which when increased, renders these materials non-porous. However, the more sterically demanding ligand L1Me gives a material that shows gate-opening behaviour in response to a CO2 absorbate. The synthesis and structure of an unexpected mixed-valence CuII/CuI 3D MOF, Cu3[Cu(L2Me)2]2(H2O)4]·xS (Cu5(L2Me)4), containing an unusual trimeric CuII node are also reported.

Artificial photosynthesis: understanding water splitting in nature.

In the context of a global artificial photosynthesis (GAP) project, we review our current work on nature's water splitting catalyst. In a recent report (Cox et al. 2014 Science 345, 804-808 (doi:10.1126/science.1254910)), we showed that the catalyst-a Mn4O5Ca cofactor-converts into an 'activated' form immediately prior to the O-O bond formation step. This activated state, which represents an all Mn(IV) complex, is similar to the structure observed by X-ray crystallography but requires the coordination of an additional water molecule. Such a structure locates two oxygens, both derived from water, in close proximity, which probably come together to form the product O2 molecule. We speculate that formation of the activated catalyst state requires inherent structural flexibility. These features represent new design criteria for the development of biomimetic and bioinspired model systems for water splitting catalysts using first-row transition metals with the aim of delivering globally deployable artificial photosynthesis technologies.

Structural Insights into tRNA Dynamics on the Ribosome.

High-resolution structures at different stages, as well as biochemical, single molecule and computational approaches have highlighted the elasticity of tRNA molecules when bound to the ribosome. It is well acknowledged that the inherent structural flexibility of the tRNA lies at the heart of the protein synthesis process. Here, we review the recent advances and describe considerations that the conformational changes of the tRNA molecules offer about the mechanisms grounded in translation.

NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins.

Intrinsically disordered proteins (IDPs) are characterized by substantial conformational flexibility and thus not amenable to conventional structural biology techniques. Given their inherent structural flexibility NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This chapter will summarize key advances in NMR methodology. Despite the availability of efficient (multi-dimensional) NMR experiments for signal assignment of IDPs it is discussed that NMR of larger and more complex IDPs demands spectral simplification strategies capitalizing on specific isotope-labeling strategies. Prototypical applications of isotope labeling-strategies are described. Since IDP-ligand association and dissociation processes frequently occur on time scales that are amenable to NMR spectroscopy we describe in detail the application of CPMG relaxation dispersion techniques to studies of IDP protein binding. Finally, we demonstrate that the complementary usage of NMR and EPR data provide a more comprehensive picture about the conformational states of IDPs and can be employed to analyze the conformational ensembles of IDPs.

Substrate Integrated Waveguide Filters: Design Techniques and Structure Innovations

Because of the inherent structural flexibility in coupling design and topological arrangement, substrate integrated waveguide (SIW) filter topologies enjoy better out-of-band frequency selectivity and/or in-band phase response with the allocation of finite transmission zeros (FTZs). In the first article in this series, basic design rules and fundamental electrical characteristics have been presented that indicate the superior performances of SIW structures and their filter applications. Advanced design techniques and innovative structure features have recently been reported in a large number of publications. They include cross couplings realized by physical and nonphysical paths and SIW filters with dual-mode or multimode techniques. Miniaturization-enabled techniques including low-temperature cofired ceramic (LTCC) technology have been developed and applied to the development of SIW filters to reduce the size for low-gigahertz applications using nontransverse electromagnetic (non-TEM) modes. Wideband SIW filters, multiband SIW filters, and reconfigurable SIW filters have also been reported by various research groups. This article reviews these advanced and innovative SIW filter technologies, and related examples are presented and discussed.

EPR-aided approach for solution structure determination of large RNAs or protein-RNA complexes.

High-resolution structural information on RNA and its functionally important complexes with proteins is dramatically underrepresented compared with proteins but is urgently needed for understanding cellular processes at the molecular and atomic level. Here we present an EPR-based protocol to help solving large RNA and protein-RNA complex structures in solution by providing long-range distance constraints between rigid fragments. Using enzymatic ligation of smaller RNA fragments, large doubly spin-labelled RNAs can be obtained permitting the acquisition of long distance distributions (>80 Å) within a large protein-RNA complex. Using a simple and fast calculation in torsion angle space of the spin-label distributions with the program CYANA, we can derive simple distance constraints between the spin labels and use them together with short-range distance restraints derived from NMR to determine the structure of a 70 kDa protein-RNA complex composed of three subcomplexes.

NMR contributions to structural dynamics studies of intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity. Given their inherent structural flexibility X-ray crystallography is not applicable to study these proteins. In contrast, NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This article will summarize key advances in basic physical-chemistry and NMR methodology, outline their limitations and envision future R&D directions.