DIAD-Dual Imaging and Diffraction Beamline
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Diamond Proposal Number(s):
[33351]
Abstract: Engineering materials selection requires a balance between mechanical strength, environmental impact, and cost-effectiveness. Wood presents distinct advantages, including economy, renewability, and low density. However, the low absolute strength and inherent susceptibility of wood to moisture significantly limit its applications in various engineering fields. Here, the reinforcing effect of cellulose fibers and the advantages of the natural porous structure of wood are significantly enhanced by the combination of densification and alkali treatment. With increased alkali treatment time to remove lignin, the tensile strength of densified pine increased to a maximum of 131 MPa (5 times that of natural pine) and then decreased. The specific energy absorption of the densified wood honeycomb structures is twice that of an engineered aluminum honeycomb, and the wood can be successfully molded into structural components through the regulation of cell wall microstructure for tailored mechanical properties.
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Nov 2026
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I03-Macromolecular Crystallography
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Abstract: The receptor tyrosine kinase cKIT plays a pivotal role in a variety of physiological processes and is implicated in a broad spectrum of pathological conditions. Its activity is controlled by phosphorylation-dependent conformational changes, which also influence the binding mode of small-molecule inhibitors. We employed an integrated experimental and computational strategy to characterize the conformational landscape of cKIT and to elucidate the binding mechanisms of four inhibitors, Avapritinib, Olverembatinib, Labuxtinib and Cenisertib. A combination of Surface Plasmon Resonance (SPR), enzymatic assay, Molecular Dynamics (MD) simulations, stability energy evaluation, Limited Proteolysis coupled to Mass Spectrometry (LiP-MS) and X-Ray crystallography was used to investigate both active and inactive kinase states. Avapritinib preferentially binds the active form of cKIT, as supported by SPR kinetics, LiP-MS patterns, and MD results. Structural data further confirm that this compound occupies the ATP-binding pocket, consistent with a Type I inhibitor. Olverembatinib and Labuxtinib exhibit high affinity for the inactive kinase, showing stronger binding to the inactive form by SPR and inducing extensive protection of residues spanning the ATP-binding pocket in LiP-MS experiment. MD analysis reveals the burial of key pocket residues, supporting a Type II inhibition mode. Cenisertib exhibits a more complex behavior. While SPR indicates binding to both kinase states, LiP-MS, MD and X-Ray crystallography analyses reveal distinct interaction patterns depending on phosphorylation. Overall, this work highlights how distinct inhibitors exploit different conformational states of cKIT and demonstrates the value of integrating structural analyses, biophysical measurements, calculations and molecular simulations to define the mechanism of kinase inhibition.
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Aug 2026
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I04-1-Macromolecular Crystallography (fixed wavelength)
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Open Access
Abstract: Odorant-binding proteins (OBPs) in mosquitoes play central roles in chemosensory perception and are attractive targets for vector control strategies. However, some OBPs are also expressed in non-olfactory tissues, suggesting a pleiotropic function that has not been sufficiently investigated. The crystal structures of the pleiotropic AgamOBP9 of the Anopheles gambiae mosquito were determined in complex with three plant-derived bioactive molecules: the phenylpropanoids n-butyl cinnamate and methyl eugenol (ME), as well as the monoterpene p-menthane-3, 8-diol (PMD). Fluorescence competitive binding assays and binding free-energy calculations identified that n-butyl cinnamate and ME bind with Ki values in the micromolar range, in contrast to the weak affinity observed for PMD. Structural analysis revealed an extended internal cavity comprising two distinct ligand-binding regions. One region, located at the bottom of the cavity, accommodated all investigated ligands without undergoing significant conformational changes, suggesting a structurally preordered binding pocket. The second region, situated at the cavity entrance, binds MPD and PEG, both used as crystallization agents, and may therefore serve as a recognition site for molecules with diverse chemical features. In the AgamOBP9–butyl cinnamate–MPD complex, MPD binding to the entrance-site induces rearrangements of surrounding residues, including Arg8, Arg15, Tyr32, Lys33, and Trp35. These interactions appear to promote the convergence of helices α1, α2, and the α2-α3 connecting loop toward a more “closed” protein conformation. The conformational flexibility of AgamOBP9 at the entrance region was further supported by differential scanning calorimetry and molecular dynamics simulations, which suggested the presence of two independent thermodynamic domains within the protein. Structural superposition with the homologous AaegOBP22–linoleic acid complex indicated that the AgamOBP9 cavity could accommodate fatty acids or other long-chain molecules spanning both binding regions, implying potential functions beyond conventional olfactory signaling. These findings provide new insights into the molecular basis of ligand recognition by AgamOBP9, which may guide the discovery of novel OBP9-targeting ligands.
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Aug 2026
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I22-Small angle scattering & Diffraction
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Open Access
Abstract: A series of weakly basic random copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were synthesized to investigate the influence of charge on their solution behavior. The random comonomer distribution was confirmed via 1H NMR spectroscopy by calculating reactivity ratios and monitoring reaction kinetics. Their pH-responsive behavior was characterized by acid–base titration and zeta potential analysis, revealing a direct correlation between degree of protonation and copolymer charge density. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS) studies revealed acid-induced changes in coil size and conformation, driven by intrachain electrostatic repulsion. Fitting SAXS data to a wormlike chain model combined with a polymer reference interaction site model (WLC-PRISM) enabled quantification of key parameters such as Kuhn length, interaction strength, and effective interaction distance to investigate the backbone flexibility and charge interactions. Higher degree of protonation led to more rigid, expanded coils, while salt screening reduced electrostatic interactions and coil dimensions. Concentration-dependent structural analysis highlighted interchain repulsion in the dilute regime, and structure factor scaling agreed with prior polyelectrolyte studies. Gel Permeation Chromatography – Multi-Angle Laser Light Scattering (GPC-MALLS) confirmed charge-induced coil swelling across a range of molecular weights. In summary, a WLC-based framework, when combined with PRISM-type interaction terms, provides a consistent and physically meaningful description of chain conformation for this class of weakly charged random copolymers within the explored pH, ionic strength, and concentration ranges.
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Jul 2026
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I04-1-Macromolecular Crystallography (fixed wavelength)
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Abstract: Plant lectins are carbohydrate-binding proteins with diverse biological functions and growing biomedical relevance due to their ability to recognize specific glycan structures. Here, we report the high-resolution crystallographic structure of a lectin from D. altissima seeds (DAL), resolved by X-ray diffraction at 2.21 Å (PDB ID: 7LJG). The structure reveals a homodimeric fold consistent with other lectins from the Dioclea genus, reinforcing its conserved molecular architecture. Other lectins reported within the Dioclea genus share the conserved β-sandwich fold typical of this group, while DAL exhibits unique amino acid substitutions at the carbohydrate-binding site that may influence its flexibility and interaction with other proteins. To explore DAL's potential antiviral activity against SARS-CoV-2, we performed molecular docking and molecular dynamics simulations targeting the main viral protease (Mpro). The results indicated that DAL forms a stable complex with Mpro, engaging key residues within the active site and exhibiting stronger predicted binding affinity than Nirmatrelvir, the currently approved COVID-19 therapeutic. Together, these findings highlight DAL as a promising scaffold for antiviral drug development, bridging structural insights and computational analysis to guide future experimental exploration.
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Jul 2026
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[34182]
Open Access
Abstract: Protein kinases regulate essential cellular processes such as apoptosis, proliferation, and growth. Precise regulation of kinase activity is critical for proper signal transduction and is often mediated by activation-loop phosphorylation. Janus kinases (JAKs) employ a unique regulatory mechanism: they remain autoinhibited by their pseudokinase domains until cytokine stimulation triggers dimerization and trans-phosphorylation of two activation-loop tyrosines. Despite its relevance for JAK inhibitor design, the molecular mechanism of JAK activation by activation-loop phosphorylation is not fully understood. Here, we show that phosphorylation of the JAK2 activation loop is essential for stabilizing substrate binding and in the absence of phosphorylation, the activation loop fails to bind substrates. Our findings reveal a unique regulatory role for the activation loop in JAK2, where phosphorylation enhances loop stability rather than inducing a major conformational change as in most protein kinases. In addition, the flexibility of the unphosphorylated activation loop allows conformational changes required for trans-phosphorylation during JAK activation. These insights provide a mechanistic basis for JAK activation and offer new insights for the development of JAK inhibitors.
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Jul 2026
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labSAXS-Offline SAXS and Sample Environment Development
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Diamond Proposal Number(s):
[39236]
Open Access
Abstract: Designing polymers that combine performance with sustainability remains a critical challenge. Here, we report high-performance elastomers derived from CO2 and biobased monomers that integrate both mechanical toughness and closed-loop chemical recyclability through a single material feature: dynamic metal–ionomer cross-links. These ABA block polymers, synthesized from ε-decalactone, δ-jasmolactone, CO2, and bicyclic epoxides, incorporate abundant and inexpensive metal carboxylates (Na(I), Zn(II), and Al(III)) into the midblock, forming reversible networks that enhance tensile strength by 150% while maintaining high strain at break (>1500%) and elastic recovery (>85%). The same cross-links act as built-in catalysts, enabling energy-efficient depolymerization of both polyester and polycarbonate domains at 200 °C, recovering the original monomers. This dual-function approach advances circular polymer design by combining enhanced performance with efficient, low-energy, closed-loop recycling.
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Mar 2026
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I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[36690]
Abstract: The online structure development during tenter-frame biaxial stretching of linear low-density (LLDPE), high-density polyethylene (HDPE), and their 50/50 blend was investigated using synchrotron Wide-Angle X-ray Scattering (WAXS). During stretching, crystallite reorientation, crystallographic slip phenomena activated at yielding, and lamellar fragmentation at higher strains are responsible for a decrease in crystallinity. These processes induce a morphological transformation from the initial semisolid spherulitic morphology into an oriented fibrillar network with lamellae in edge-on orientation, and the b- and c-axes constrained within the film plane, as confirmed by ex-situ WAXS and SAXS. These phenomena are more important for HDPE, which exhibits higher susceptibility to biaxial stretching. Upon cooling, the morphology developed during stretching is preserved, as newly crystallized material grows epitaxially on the preexisting structure. These findings highlight the higher structural sensitivity of HDPE during semisolid biaxial stretching compared with LLDPE, providing unique information to understand and control the biaxial processing of polyethylene.
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Mar 2026
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B21-High Throughput SAXS
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Diamond Proposal Number(s):
[36130]
Open Access
Abstract: The initiation of allergic responses critically depends on the recognition of an allergenic epitope by the paratope of IgE antibodies. While previous structural studies have focused on recombinant fragments or engineered forms of IgE, the structure of full-length IgE in its native state remains poorly understood. In this study, we investigate the conformational changes of a native murine IgE (2F5), both in its free form and upon binding to the Hevea brasiliensis allergen profilin (Hev b 8). Small-angle X-ray scattering (SAXS) data reveal that unbound IgE adopts an extended conformation with open Fab arms. However, when it binds to profilin, it transitions to a more compact arrangement characterized by closer proximity of the arms. Molecular dynamics (MD) simulations of the Fab region further identified conformational rearrangements upon allergen binding, including a twisting motion and partial disruption of interactions between the naturally paired heavy and light chains. These findings indicate that there may be allosteric communication between Fab and Fc regions, even in the absence of a hinge region, which is not present in IgE. Overall, this study provides valuable insights into the dynamic structural properties of native IgE and enhances our understanding of the molecular mechanisms underlying allergen recognition.
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Nov 2025
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B21-High Throughput SAXS
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Diamond Proposal Number(s):
[33176, 35926]
Open Access
Abstract: Mycobacterial infections, including tuberculosis, remain a major global health challenge, causing millions of deaths annually. Their treatment is increasingly hindered by limited therapeutic options and rising antimicrobial resistance, highlighting the urgent need for alternative strategies. Mycobacteriophage LysA endolysins are complex multi-domain peptidoglycan hydrolases emerging as potential tools to treat mycobacterial infections. However, despite the therapeutic prospects of LysAs, our understanding of their mechanism of action remains limited. This study provides a comprehensive structural-functional analysis of the catalytic domains of D29LysA and DS6ALysA endolysins (D29N4/D29GH19 and DS6AGH19/DS6AAmi2B), characterised alone and in complex with PG analogues, using protein engineering, X-ray crystallography, small-angle X-ray scattering, and in silico tools. Our results reveal precise details of the substrate-binding site and the catalytic platforms at each domain, including information about substrate-binding mode and conformational changes associated with peptidoglycan recognition and hydrolysis. Moreover, these findings also suggest a coordinated mechanism of action of both catalytic domains in DS6ALysA lysin. These insights represent a significant advance in understanding the structural basis of mycobacterial cell-wall degradation by mycobacteriophage endolysins. Information that may aid in further exploring these endolysins as therapeutic antimicrobial tools in the future.
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Nov 2025
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