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At least 1,369 records · Page 76

Structural insights on ligand recognition at the human leukotriene B4 receptor 1

The leukotriene B4 receptor 1 (BLT1) regulates the recruitment and chemotaxis of different cell types and plays a role in the pathophysiology of infectious, allergic, metabolic, and tumorigenic human diseases. Here we present a crystal structure of human BLT1 (hBLT1) in complex with a selective antagonist MK-D-046, developed for the treatment of type 2 diabetes and other inflammatory conditions. Comprehensive analysis of the structure and structure-activity relationship data, reinforced by site-directed mutagenesis and docking studies, reveals molecular determinants of ligand binding and selectivity toward different BLT receptor subtypes and across species. The structure helps to identify a putative membrane-buried ligand access channel as well as potential receptor binding modes of endogenous agonists. These structural insights of hBLT1 enrich our understanding of its ligand recognition and open up future avenues in structure-based drug design.

59 BASIC BIOLOGICAL SCIENCES↗

Geometry of the charge density wave in the kagome metal A V 3 Sb 5

Kagome lattice is a fertile platform for topological and intertwined electronic excitations. Recently, experimental evidence of an unconventional charge density wave (CDW) is observed in a Z 2 kagome metal AV 3 Sb 5 (A=K, Cs, Rb). This observation triggers wide interest in the interplay between frustrated crystal structure and Fermi surface instabilities. Here, we analyze the lattice effect and its impact on CDW in AV 3 Sb 5 . Based on published experimental data, we show that the 2×2×2 CDW breaks the sixfold rotational symmetry of the crystal due to the phase shift between kagome layers and can explain the twofold symmetric CDW peak intensity observed by scanning tunneling spectroscopy. The coupling between the lattice and electronic degrees of freedom yields a weak first-order structural transition without continuous change of lattice dynamics. Our result emphasizes the fundamental role of lattice geometry in proper understanding of unconventional electronic orders in AV 3 Sb 5 .

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Structural insights into the unique recognition module between α-synuclein peptide and nanobody

Nanobodies are single-domain fragments of antibodies with comparable specificity and affinity to antibodies. They are emerging as versatile tools in biology due to their relatively small size. Here, we report the crystal structure of a specific nanobody Nbα-syn01, bound to a 14 amino acid long peptide of α-synuclein (αSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. The complex structure exhibits a unique binding pattern where the αSyn peptide replaces the N-terminal region of nanobody. Recognition is mediated principally by extended main chain interaction of the αSyn peptide and specificity of the interaction lies in the central 48–52 region of αSyn peptide. Structure-guided truncation of Nbα-syn01 shows tighter binding to αSyn peptide and improved inhibition of α-synuclein aggregation. The structure of the truncated complex was subsequently determined and was indistinguishable to full length complex as the full-length form had no visible electron density for the N-terminal end. These findings reveal the molecular basis for a previously unobserved binding mode for nanobody recognition of α-synuclein, providing an explanation for the enhanced binding, and potential for an alternate framework for structure-based protein engineering of nanobodies to develop better diagnostic and therapeutic tools.

59 BASIC BIOLOGICAL SCIENCES↗

Structural and functional analyses of the echinomycin resistance conferring protein Ecm16 from Streptomyces lasalocidi

Echinomycin is a natural product DNA bisintercalator antibiotic. The echinomycin biosynthetic gene cluster in Streptomyces lasalocidi includes a gene encoding the self-resistance protein Ecm16. Here, we present the 2.0 Å resolution crystal structure of Ecm16 bound to adenosine diphosphate. The structure of Ecm16 closely resembles that of UvrA, the DNA damage sensor component of the prokaryotic nucleotide excision repair system, but Ecm16 lacks the UvrB-binding domain and its associated zinc-binding module found in UvrA. Mutagenesis study revealed that the insertion domain of Ecm16 is required for DNA binding. Furthermore, the specific amino acid sequence of the insertion domain allows Ecm16 to distinguish echinomycin-bound DNA from normal DNA and link substrate binding to ATP hydrolysis activity. Expression of ecm16 in the heterologous host Brevibacillus choshinensis conferred resistance against echinomycin and other quinomycin antibiotics, including thiocoraline, quinaldopeptin, and sandramycin. Our study provides new insight into how the producers of DNA bisintercalator antibiotics fend off the toxic compounds that they produce.

59 BASIC BIOLOGICAL SCIENCES↗

Correlation of optical properties with particle size, morphology, and polymorph of fine- and nano-particle formulations of titanium dioxide powders

Titanium dioxide (TiO 2 ) particulates are known to exhibit different visible and infrared optical properties compared to the bulk material, showing strong dependence on particle size, crystal structure, and morphology. In this study, the optical properties, sizes, and morphologies of TiO 2 particles from two different sources (nano and fine powders) having a) nominally different particle sizes and b) various crystal polymorph mixture fractions are compared using a combination of single particle mass spectrometry, optical spectroscopies, and aerosol characterization methods. The nano sample was found to be largely particles of the anatase polymorph (88% by mass), while the fine sample was found to consist largely of rutile particles (95% by mass). Two distinct particle morphologies (fractal and compact) were found in each powder sample and could be identified and separated in-situ based on particle aerodynamic properties. The attenuation of near-infrared, visible and ultraviolet light by TiO 2 particles shows strong dependence on particle morphology. Furthermore, while the fine particles were found to have larger near-infrared (675–800 nm) extinction coefficients by mass than the nanoparticles, the reverse was true in the ultraviolet and visible regions (370–675 nm). However, for polydisperse particles with different sizes and shapes, the optical behaviors are not straightforward to directly correlate to a combination of physical parameters.

Lockwood, Schuyler P. [Pacific Northwest National ↗

Structure of the E. coli nucleoid-associated protein YejK reveals a novel DNA binding clamp

Abstract Nucleoid-associated proteins (NAPs) play central roles in bacterial chromosome organization and DNA processes. The Escherichia coli YejK protein is a highly abundant, yet poorly understood NAP. YejK proteins are conserved among Gram-negative bacteria but show no homology to any previously characterized DNA-binding protein. Hence, how YejK binds DNA is unknown. To gain insight into YejK structure and its DNA binding mechanism we performed biochemical and structural analyses on the E. coli YejK protein. Biochemical assays demonstrate that, unlike many NAPs, YejK does not show a preference for AT-rich DNA and binds non-sequence specifically. A crystal structure revealed YejK adopts a novel fold comprised of two domains. Strikingly, each of the domains harbors an extended arm that mediates dimerization, creating an asymmetric clamp with a 30 Å diameter pore. The lining of the pore is electropositive and mutagenesis combined with fluorescence polarization assays support DNA binding within the pore. Finally, our biochemical analyses on truncated YejK proteins suggest a mechanism for YejK clamp loading. Thus, these data reveal YejK contains a newly described DNA-binding motif that functions as a novel clamp.

Biochemistry & Molecular Biology↗

Vertical and Lateral Etch Survey of Ferroelectric AlN/Al 1-x Sc x N in Aqueous KOH Solutions

Due to their favorable electromechanical properties, such as high sound velocity, low dielectric permittivity and high electromechanical coupling, Aluminum Nitride (AlN) and Aluminum Scandium Nitride (Al 1-x Sc x N) thin films have achieved widespread application in radio frequency (RF) acoustic devices. The resistance to etching at high scandium alloying, however, has inhibited the realization of devices able to exploit the highest electromechanical coupling coefficients. In this work, we investigated the vertical and lateral etch rates of sputtered AlN and Al 1-x Sc x N with Sc concentration x ranging from 0 to 0.42 in aqueous potassium hydroxide (KOH). Etch rates and the sidewall angles were reported at different temperatures and KOH concentrations. We found that the trends of the etch rate were unanimous: while the vertical etch rate decreases with increasing Sc alloying, the lateral etch rate exhibits a V-shaped transition with a minimum etch rate at x = 0.125. By performing an etch on an 800 nm thick Al 0.875 Sc 0.125 N film with 10 wt% KOH at 65 °C for 20 min, a vertical sidewall was formed by exploiting the ratio of the {$10\overline{11}$ planes and {$1\overline{1}00$ planes etch rates. This method does not require preliminary processing and is potentially beneficial for the fabrication of lamb wave resonators (LWRs) or other microelectromechanical systems (MEMS) structures, laser mirrors and Ultraviolet Light-Emitting Diodes (UV-LEDs). It was demonstrated that the sidewall angle tracks the trajectory that follows the {$\overline{1}2\overline{12}$ of the hexagonal crystal structure when different c/a ratios were considered for elevated Sc alloying levels, which may be used as a convenient tool for structure/composition analysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception

The vertebrate inner ear, responsible for hearing and balance, is able to sense minute mechanical stimuli originating from an extraordinarily broad range of sound frequencies and intensities or from head movements. Integral to these processes is the tip-link protein complex, which conveys force to open the inner-ear transduction channels that mediate sensory perception. Protocadherin-15 and cadherin-23, two atypically large cadherins with 11 and 27 extracellular cadherin (EC) repeats, are involved in deafness and balance disorders and assemble as parallel homodimers that interact to form the tip link. Here we report the X-ray crystal structure of a protocadherin-15 + cadherin-23 heterotetrameric complex at 2.9-Å resolution, depicting a parallel homodimer of protocadherin-15 EC1-3 molecules forming an antiparallel complex with two cadherin-23 EC1-2 molecules. In addition, we report structures for 10 protocadherin-15 fragments used to build complete high-resolution models of the monomeric protocadherin-15 ectodomain. Molecular dynamics simulations and validated crystal contacts are used to propose models for the complete extracellular protocadherin-15 parallel homodimer and the tip-link bond. Steered molecular dynamics simulations of these models suggest conditions in which a structurally diverse and multimodal protocadherin-15 ectodomain can act as a stiff or soft gating spring. These results reveal the structural determinants of tip-link–mediated inner-ear sensory perception and elucidate protocadherin-15’s structural and adhesive properties relevant in disease.

59 BASIC BIOLOGICAL SCIENCES↗

Techniques for studying materials under extreme states of high energy density compression

The properties of materials under extreme conditions of pressure and density are of key interest to a number of fields, including planetary geophysics, materials science, and inertial confinement fusion. In geophysics, the equations of state of planetary materials, such as hydrogen and iron, under ultrahigh pressure and density provide a better understanding of their formation and interior structure [Celliers et al., “Insulator-metal transition in dense fluid deuterium,” Science 361, 677–682 (2018) and Smith et al., “Equation of state of iron under core conditions of large rocky exoplanets,” Nat. Astron. 2, 591–682 (2018)]. The processes of interest in these fields occur under conditions of high pressure (100 GPa–100 TPa), high temperature (>3000 K), and sometimes at high strain rates (>103 s−1) depending on the process. With the advent of high energy density (HED) facilities, such as the National Ignition Facility (NIF), Linear Coherent Light Source, Omega Laser Facility, and Z, these conditions are reachable and numerous experimental platforms have been developed. To measure compression under ultrahigh pressure, stepped targets are ramp-compressed and the sound velocity, measured by the velocity interferometer system for any reflector diagnostic technique, from which the stress-density of relevant materials is deduced at pulsed power [M. D. Knudson and M. P. Desjarlais, “High-precision shock wave measurements of deuterium: Evaluation of exchange-correlation functionals at the molecular-to-atomic transition,” Phys. Rev. Lett. 118, 035501 (2017)] and laser [Smith et al., “Equation of state of iron under core conditions of large rocky exoplanets,” Nat. Astron. 2, 591–682 (2018)] facilities. To measure strength under high pressure and strain rates, experimenters measure the growth of Rayleigh–Taylor instabilities using face-on radiography [Park et al., “Grain-size-independent plastic flow at ultrahigh pressures and strain rates,” Phys. Rev. Lett. 114, 065502 (2015)]. The crystal structure of materials under high compression is measured by dynamic x-ray diffraction [Rygg et al., “X-ray diffraction at the national ignition facility,” Rev. Sci. Instrum. 91, 043902 (2020) and McBride et al., “Phase transition lowering in dynamically compressed silicon,” Nat. Phys. 15, 89–94 (2019)]. Medium range material temperatures (a few thousand degrees) can be measured by extended x-ray absorption fine structure techniques, Yaakobi et al., “Extended x-ray absorption fine structure measurements of laser-shocked V and Ti and crystal phase transformation in Ti,” Phys. Rev. Lett. 92, 095504 (2004) and Ping et al., “Solid iron compressed up to 560 GPa,” Phys. Rev. Lett. 111, 065501 (2013), whereas more extreme temperatures are measured using x-ray Thomson scattering or pyrometry. This manuscript will review the scientific motivations, experimental techniques, and the regimes that can be probed for the study of materials under extreme HED conditions.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Effect of Mg Content in Melt-Spun Mn–Bi–Mg–Sb–In Alloys on the Structure and Properties of Field-Annealed Magnets

Mn-Bi alloys modified with Mg and other elements were recently developed into promising rare-earth-free permanent magnets through successive melt-spinning, warm compaction, and short magnetic-field annealing. This letter reports herein on the crystal structures, texture, and magnetic properties observed in Mn 50 Bi 49-x Mg x Sb 0.5 In 0.5 alloys (x = 0, 1.5, 3.0, 4.5) throughout these processing steps. The Mg substitution favors MnBi-based intermetallic phases over the Bi- and Mn-based solid solutions and the stable α intermetallic phase over the metastable β' intermetallic phase. Magnesium increases the c/a ratio of the α phase lattice parameters for all studied x values and it increases the degree of the field-annealing-induced texture for x ≤ 3. The effect of Mg on coercivity is explained as combination of a positive one via the α phase magnetocrystalline anisotropy and a negative one via the development of texture. The effect of the substitution on the maximum energy product additionally involves the decreasing density of the alloys; the optimum x is found to be ≈3. Additionally reported are the thermal properties of selected alloys. The mechanism of field-annealing effect on the coercivity is briefly discussed.

36 MATERIALS SCIENCE↗

Role of Postdeposition Thermal Annealing on Intracrystallite and Intercrystallite Structuring and Charge Transport in Poly(3-hexylthiophene)

The performance of electronic devices comprising conjugated polymers as the active layer depends not only on the intrinsic characteristics of the materials but also on the details of the extrinsic processing conditions. Here, we examine the effect of postdeposition thermal treatments on the microstructure of poly(3-hexylthiophene) (P3HT) thin films and its impact on their electrical properties. Unsurprisingly, we find thermal annealing of P3HT thin films to generally increase their crystallinity and crystallite coherence length while retaining the same crystal structure. Despite such favorable structural improvements of the polymer active layers, however, thermal annealing at high temperatures can lead to a net reduction in the mobility of transistors, implicating structural changes in the intercrystallite amorphous regions of these semicrystalline active layers take place on annealing, and the simplistic picture that crystallinity governs charge transport is not always valid. Our results instead suggest tie-chain pullout, which occurs during crystal growth and perfection upon thermal annealing to govern charge transport, particularly in low-molecular-weight systems in which the tie-chain fraction is low. By demonstrating the interplay between intracrystallite and intercrystallite structuring in determining the macroscopic charge transport, we shed light on how structural evolution and charge-transport properties of nominally the same polymer can vary depending on the details of processing.

36 MATERIALS SCIENCE↗

Deconvolution of X-ray natural and magnetic circular dichroism in chiral Dy-ferroborate

Structural chirality and magnetism, when intertwined, can have profound implications on materials properties. Using X-ray imaging and spectroscopic measurements that leverage the natural and magnetic circular dichroic effects present in magnetized chiral crystal structures, we probe the interplay between chirality and magnetism across the field-induced spin-flop transition of Dy ferroborate, DyFe 3 (BO 3 ) 4 . Deconvolution of natural and magnetic circular dichroic signals at the Fe K and Dy L 2,3 absorption edges of the non-centrosymmetric structure was enabled by use of tunable temperature and magnetic field, providing access to element-specific magnetic information across the spin-flop transition. The magnetic response of Fe and Dy sublattices was found to be independent of domain chirality. The chiral domains were robust against both the (chirality preserving) R32 to P3 1 21/P3 2 21 structural phase transition at 280 K, and application of magnetic field up to 4 Tesla. A third flavor of X-ray dichroism, magneto-chiral dichroism, was not detected within the accuracy of our measurements. The absence of significant Fe magnetization along the screw, c-axis for the magnetic field strength used in this study, together with non-linear coupling of magnetic field to electric polarization across the spin-flop transition, may hinder observation of magneto-chiral dichroic effects in this system.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Three-dimensional checkerboard spin structure on a breathing pyrochlore lattice

The standard approach to realize a spin-liquid state is through magnetically frustrated states, relying on ingredients such as the lattice geometry, dimensionality, and magnetic interaction type of the spins. While Heisenberg spins on a pyrochlore lattice with only antiferromagnetic nearest-neighbor interactions are theoretically proven disordered, spins in real systems generally include longer-range interactions. The spatial correlations at longer distances typically stabilize a long-range order rather than enhancing a spin-liquid state. Both states can, however, be destroyed by short-range static correlations introduced by chemical disorder. Here, using disorder-free specimens with a clear long-range antiferromagnetic order, we refine the spin structure of the Heisenberg spinel ZnFe 2 O 4 through neutron magnetic diffraction. The unique wave vector (1, 0, $\frac{1}{2}$) leads to a spin structure that can be viewed as alternatively stacked ferromagnetic and antiferromagnetic tetrahedra in a three-dimensional checkerboard form. Stable coexistence of these opposing types of clusters is enabled by the bipartite breathing pyrochlore crystal structure, leading to a second-order phase transition at 10 K. The diffraction intensity of ZnFe 2 O 4 is an exact complement to the inelastic scattering intensity of several chromate spinel systems which are regarded as model classical spin liquids. Our results challenge this attribution, and suggest instead of the six-spin ring mode, spin excitations in chromate spinels are closely related to the (1, 0, $\frac{1}{2}$) type of spin order and the four-spin ferromagnetic cluster locally at one tetrahedron.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Defect graph neural networks for materials discovery in high-temperature clean-energy applications

We present a graph neural network approach that fully automates the prediction of defect formation enthalpies for any crystallographic site from the ideal crystal structure, without the need to create defected atomic structure models as input. Here we used density functional theory reference data for vacancy defects in oxides, to train a defect graph neural network (dGNN) model that replaces the density functional theory supercell relaxations otherwise required for each symmetrically unique crystal site. Interfaced with thermodynamic calculations of reduction entropies and associated free energies, the dGNN model is applied to the screening of oxides in the Materials Project database, connecting the zero-kelvin defect enthalpies to high-temperature process conditions relevant for solar thermochemical hydrogen production and other energy applications. The dGNN approach is applicable to arbitrary structures with an accuracy limited principally by the amount and diversity of the training data, and it is generalizable to other defect types and advanced graph convolution architectures. In conclusion, it will help to tackle future materials discovery problems in clean energy and beyond.

97 MATHEMATICS AND COMPUTING↗

Interplay of coulomb and exciton–phonon coupling controls singlet fission dynamics in two pentacene polymorphs

Pentacene is an important model organic semiconductor in both the singlet exciton fission (SF) and organic electronics communities. We have investigated the effect of changing crystal structure on the SF process, generating multiple triplet excitons from an initial singlet exciton, and subsequent triplet recombination. Unlike for similar organic semiconductors that have strong SF sensitive to polymorphism, we find almost no quantitative difference between the kinetics of triplet pair (TT) formation in the two dominant polymorphs of pentacene. Both pairwise dimer coupling and momentum-space crystal models predict much faster TT formation from the bright singlet excited state of the Bulk vs ThinFilm polymorph, contrasting with the experiment. GW and Bethe–Salpeter equation calculations, including exciton–phonon coupling, reveal that ultrafast phonon-driven transitions in the ThinFilm polymorph compensate the intrinsically slower purely Coulomb-mediated TT formation channel, rationalizing the similarity in observed rates. Taking into account the influence of subtle structural distinctions on both the direct and phonon-mediated SF pathways reveals a predictive capability to these methods, expected to be applicable to a wide variety of molecular crystals.

14 SOLAR ENERGY↗

In situ Formation of Platinum-Carbon Catalysts in Propane Dehydrogenation

The catalytic production of propylene via propane dehydrogenation (PDH) is a key reaction in the chemical industry. By combining operando transmission electron microscopy with density functional theory analysis, we show that the intercalation and ordering of carbon on Pt interstitials to form Pt-C solid solutions is relevant for increasing propylene production. More specifically, we found that at the point of enhanced propylene formation, the structure of platinum nanoparticles is transformed into a transient caesium chloride-type Pt-C polymorph. At more elevated temperatures, the zincblende and rock salt polymorphs seemingly coexist. When propylene production was highest, multiple crystal structures consisting of Pt and carbon were occasionally found to coexist in one individual nanoparticle, distorting the Pt lattice. Catalyst coking was detected at all stages of the reaction, but did initially not affect all particles. These findings could lead to the development of novel synthesis strategies towards tailoring highly efficient PDH catalysts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗