Browsing by Author "Sokolova, AV"

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    Behaviour of single transmembrane peptides during in meso crystallization from the contrast-matched lipidic cubic phase of monoolein
    (Australian Institute of Nuclear Science and Engineering (AINSE), 2018-11-19) van't Hag, L; de Campo, L; Tran, N; Sokolova, AV; Trenker, R; Call, M; Garvey, CJ; Leung., A; Darwish, TA; Krause-Heuer, AM; Knott, RB; Meikle, T; Gras, S; Drummond, CJ; Mezzenga, R; Conn, C
    In meso membrane protein crystallization within a lipidic mesophase has revolutionized the structural biology of integral membrane proteins (IMPs). High-resolution structures of these proteins are crucial to understanding fundamental cellular processes at a molecular level, and can lead to new and improved treatments for a wide range of diseases via rational drug design. However, overall success rates of the promising in meso crystallization technique remain low because of a fundamental lack of understanding about factors that promote crystal growth. In particular, to date, two decades from invention of the method, the protein-eye-view of the in meso crystallization mechanism had not been solved. We have investigated this for the first time using small-angle neutron scattering (SANS). Contrast-matching between the scattering of the lipid membrane formed by MO and the aqueous solution was used to isolate and track the scattering of single-transmembrane peptides during the growth of protein crystals in meso. No peptide enrichment was observed at the flat points of the diamond cubic QIID phase of MO in contrast to suggestions in several modeling studies. During in meso crystallization of the DAP12 peptide a decrease in form factor and a transient fluid lamellar Lα phase could be observed providing direct evidence for the proposed crystallization mechanism. Synthesis of fully deuterated MO was required for this purpose and scattering of this new material in various solvents and under a range of conditions will be described, specifically regarding the effect of the relative scattering length densities (SLD) of the headgroup, acyl chain and solvent, which can advance the use of neutron scattering with other self-assembly materials. © The Authors.
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    Characterization of nano sized microstructures in Ni base ODS alloys using SANS and SAXS
    (International Conference on Neutron Scattering, 2017-07-12) Han, YS; Jang, J; Sokolova, AV
    The effects of thermo-mechanical treatment on microstructure of Ni base ODS(Oxide Dispersion Strengthened)alloys for future nuclear application were studied by SANS(Small Angle Neutron Scattering) and SAXS(Small Angle X-ray Scattering). Ni base ODS alloys were manufactured by MA(Mechanical Alloying) and hot extrusion process. The SANS experiments were performed by the 40 meter SANS instrument at HANARO and the Bilby SANS instrument at ANSTO. The SAXS experiments were performed by 9A SAXS beam line at Pohang Light Source. The existing phases were identified by the electron microscope and the X-ray diffractometer. The tensile test for the ODS alloys was performed at room temperature and 700?. The nano sized microstructures such as yttrium oxides, gamma prime phase and carbides were quantitatively analyzed by SANS. Based on the difference of the SANS and SAXS intensity in absolute units, the alloy contrast variation (ACV) method were used to determine the type of nano-sized precipitates. The relationship between microstructures and mechanical properties were analyzed and the effects of thermomechanical treatments on microstructure was discussed according to the quantitative microstructural analysis results by SANS and SAXS.
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    CLIC proteins, ezrin, radixin, moesin and the coupling of membranes to the actin cytoskeleton: A smoking gun?
    (Elsevier, 2014-02-01) Jiang, L; Phang, JM; Yu, J; Harrop, SJ; Sokolova, AV; Duff, AP; Wilik, KE; Alkhamici, H; Breit, SN; Valenzuela, SM; Brown, LJ; Curmi, PMG
    The CLIC proteins are a highly conserved family of metazoan proteins with the unusual ability to adopt both soluble and integral membrane forms. The physiological functions of CLIC proteins may include enzymatic activity in the soluble form and anion channel activity in the integral membrane form. CLIC proteins are associated with the ERM proteins: ezrin, radixin and moesin. ERM proteins act as cross-linkers between membranes and the cortical actin cytoskeleton. Both CLIC and ERM proteins are controlled by Rho family small GTPases. CLIC proteins, ERM and Rho GTPases act in a concerted manner to control active membrane processes including the maintenance of microvillar structures, phagocytosis and vesicle trafficking. All of these processes involve the interaction of membranes with the underlying cortical actin cytoskeleton. The relationships between Rho GTPases, CLIC proteins, ERM proteins and the membrane:actin cytoskeleton interface are reviewed. Speculative models are proposed involving the formation of localised multi-protein complexes on the membrane surface that assemble via multiple weak interactions. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. © 2013, Elsevier B.V.
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    Correlation of thermostability and conformational changes of catechol 2, 3-dioxygenases from two disparate micro-organisms
    (Elsevier Science BV, 2013-10-01) Sokolova, AV; Huang, SL; Duff, AP; Gilbert, EP; Li, WH
    We have investigated the structure of recombinant catechol 2, 3-dioxygenase (C23O) purified from two species in which the enzyme has evolved to function at different temperature. The two species are mesophilic bacterium Pseudomonas putida strain mt-2 and thermophilic archaea Sulfolobus acidocaldarius DSM639. Using the primary sequence analysis, we show that both C23Os have only 30% identity and 48% similarity but contain conserved amino acid residues forming an active site area around the iron ion. The corresponding differences in homology, but structural similarity in active area residues, appear to provide completely different responses to heating the two enzymes. We confirm this by small angle X-ray scattering and demonstrate that the overall structure of C23O from P. putida is slightly different from its crystalline form whereas the solution scattering of C230 from S. acidocaldarius at temperatures between 4 and 85 degrees C ideally fits the calculated scattering from the single crystal structure. The thermostability of C230 from S. acidocaldarius correlates well with conformation in solution during thermal treatment. The similarity of the two enzymes in primary and tertiary structure may be taken as a confirmation that two enzymes have evolved from a common ancestor. © 2013, Elsevier Ltd.
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    Crystallographic characterization of fluorapatite glass-ceramics synthesized from industrial waste
    (Cambridge University Press, 2017-09-15) Loy, CW; Matori, KA; Zainuddin, N; Whitten, AE; Rehm, C; de Campo, L; Sokolova, AV; Schmid, S
    A series of phase transformations of a novel fluoroaluminosilicate glass forming a range of fluorapatite glass-ceramics on sintering are reported. The sintering process induces formation of fluorapatite, mullite, and anorthite phases within the amorphous silicate matrices of the glass-ceramics. The fluoroaluminosilicate glass, SiO2–Al2O3–P2O5–CaO–CaF2, is prepared from waste materials, such as rice husk ash, pacific oyster shells, and disposable aluminium cans. The thermally induced crystallographic and microstructure evolution of the fluoroaluminosilicate glass towards the fluorapatite glass-ceramics, with applications in dental and bone restoration, are investigated by powder X-ray diffraction and small-angle neutron-scattering techniques. © Cambridge University Press.
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    Design and synthesis of an azobenzene–betaine surfactant for photo-rheological fluids
    (Elsevier, 2021-07-15) Butler, CSG; King, JP; Giles, LW; Marlow, JB; Vidallon, MLP; Sokolova, AV; de Campo, L; Tuck, KL; Tabor, RF
    Hypothesis Morphology of surfactant self-assemblies are governed by the intermolecular interactions and packing constraints of the constituent molecules. Therefore, rational design of surfactant structure should allow targeting of the specific self-assembly modes, such as wormlike micelles (WLMs). By inclusion of an appropriate photo-responsive functionality to a surfactant molecule, light-based control of formulation properties without the need for additives can be achieved. Experiments A novel azobenzene-containing surfactant was synthesised with the intention of producing photo-responsive wormlike micelles. Aggregation of the molecule in its cis and trans isomers, and its concomitant flow properties, were characterised using UV–vis spectroscopy, small-angle neutron scattering, and rheological measurements. Finally, the fluids capacity for mediating particle diffusion was assessed using dynamic light scattering. Findings The trans isomer of the novel azo-surfactant was found to form a viscoelastic WLM network, which transitioned to inviscid ellipsoidal aggregates upon photo-switching to the cis isomer. This was accompanied by changes in zero-shear viscosity up to 16,000x.UV–vis spectroscopic and rheo-SANS analysis revealed interactions of the trans azobenzene chromophore within the micelles, influencing aggregate structure and contributing to micellar rigidity. Particles dispersed in a 1 wt% surfactant solution showed a fivefold increase in apparent diffusion coefficient after UV-irradiation of the mixture. Crown Copyright © 2021 Published by Elsevier Inc.
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    Dynamical transition in a large globular protein: macroscopic properties and glass transition
    (Elsevier, 2010-01) Kealley, CS; Sokolova, AV; Kearley, GJ; Kemner, E; Russina, M; Faraone, A; Hamilton, WA; Gilbert, EP
    Hydrated soy-proteins display different macroscopic properties below and above approximately 25% moisture. This is relevant to the food industry in terms of processing and handling. Quasi-elastic neutron spectroscopy of a large globular soy-protein, glycinin, reveals that a similar moisture-content dependence exists for the microscopic dynamics as well. We find evidence of a transition analogous to those found in smaller proteins, when investigated as a function of temperature, at the so-called dynamical transition. In contrast, the glass transition seems to be unrelated. Small proteins are good model systems for the much larger proteins because the relaxation characteristics are rather similar despite the change in scale. For dry samples, which do not show the dynamical transition, the dynamics of the methyl group is probably the most important contribution to the QENS spectra, however a simple rotational model is not able to explain the data. Our results indicate that the dynamics that occurs above the transition temperature is unrelated to that at lower temperatures and that the transition is not simply related to the relaxation rate falling within the spectral window of the spectrometer. © 2010, Elsevier Ltd.
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    Energy-resolved neutron imaging options at a small angle neutron scattering instrument at the Australian Center for Neutron Scattering
    (AIP Publishing, 2019-03-26) Tremsin, AS; Sokolova, AV; Salvemini, F; Luzin, V; Paradowska, AM; Muránsky, O; Kirkwood, HJ; Abbey, B; Wensrich, CM; Kisi, EH
    Energy-resolved neutron imaging experiments conducted on the Small Angle Neutron Scattering (SANS) instrument, Bilby, demonstrate how the capabilities of this instrument can be enhanced by a relatively simple addition of a compact neutron counting detector. Together with possible SANS sample surveying and location of the region of interest, this instrument is attractive for many imaging applications. In particular, the combination of the cold spectrum of the neutron beam and its pulsed nature enables unique non-destructive studies of the internal structure for samples that are opaque to other more traditional techniques. In addition to conventional white beam neutron radiography, we conducted energy-resolved imaging experiments capable of resolving features related to microstructure in crystalline materials with a spatial resolution down to ∼0.1 mm. The optimized settings for the beamline configuration were determined for the imaging modality, where the compromise between the beam intensity and the achievable spatial resolution is of key concern. © 2020 AIP Publishing LLC
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    Few-layer hexagonal boron nitride / 3D printable polyurethane composite for neutron radiation shielding applications
    (Elsevier, 2023-03) Knott, JC; Khakbaz, HS; Allen, J; Wu, L; Mole, RA; Baldwin, C; Nelson, A; Sokolova, AV; Beirne, S; Innis, PC; Frost, DG; Cortie, DL; Rule, KC
    Functional polymer composites can confer a range of benefits in practical applications that go beyond the individual properties of the constituent materials. Here we investigate and characterize the neutron absorbing capability of few-layer hexagonal boron nitride (h-BN) in composite with a 3D-printable thermoplastic polyurethane, and present experiment and simulation data to understand the processes and mechanisms in play. Shielding and protection from neutrons can be necessary in a range of terrestrial and space-based applications. The neutron absorption of composites with varying fractions of h-BN is strongly energy-dependent in the low-energy regime below 10 meV, and a composite containing 20 wt% h-BN shows a 70-fold reduction in the transmission relative to pure polyurethane at 0.5 meV neutron energies. This is attributed to the strong neutron capture cross-section of the naturally abundant boron-10 isotope, with energy-dependent measurements up to 100 meV confirming this point. Using inelastic neutron spectroscopy, we identify additional effects from the hydrogen in the polyurethane which both scatters diffusively and moderates neutrons inelastically via its phonon spectrum, enhancing the neutron absorption characteristics. Two models – based on analytic functions and Monte Carlo numerical techniques – are presented, and show excellent agreement with experiment results. The 3D-printability of the composite is demonstrated, and the opportunities and challenges for deploying these composites in neutron radiation protection applications are discussed. © 2022 Published by Elsevier Ltd.
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    Guanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: a small-angle x-ray scattering study
    (Wiley Online Library, 2013-06-4) Pham, CLL; Kirby, N; Wood, K; Ryan, T; Roberts, B; Sokolova, AV; Barnham, KJ; Masters, CL; Knott, RB; Cappai, R; Curtain, CC; Rekas, A
    Alpha-synuclein (α-syn) forms the amyloid-containing Lewy bodies found in the brain in Parkinson's disease. The neurotransmitter dopamine (DA) reacts with α-syn to form SDS-resistant soluble, non-amyloid, and melanin-containing oligomers. Their toxicity is debated, as is the nature of their structure and their relation to amyloid-forming conformers of α-syn. The small-angle X-ray scattering technique in combination with modeling by the ensemble optimization method showed that the un-reacted native protein populated three broad classes of conformer, while reaction with DA gave a restricted ensemble range suggesting that the rigid melanin molecule played an important part in their structure. We found that 6 M guanidine hydrochloride did not dissociate α-syn DA-reacted dimers and trimers, suggesting covalent linkages. The pathological significance of covalent association is that if they are non-toxic, the oligomers would act as a sink for toxic excess DA and α-syn; if toxic, their stability could enhance their toxicity. We argue it is essential, therefore, to resolve the question of whether they are toxic or not. © 2013,Wiley Periodicals, Inc.
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    Liquid crystals with hierarchical ordering
    (International Conference on Neutron Scattering, 2017-07-12) de Campo, L; Moghaddam, M; Sokolova, AV; Rehm, C; Mittelbach, R; Varslot, T; Castle, T; Garvey, CJ; Kirby, N; Hyde, ST
    We present liquid crystal geometries experimentally found for star-polyphilic molecules as the basic building block. Star-polyphiles are small molecules, bearing three mutually immiscible chains attached to a common center [1,2,3]. Like conventional lipids or surfactants (that usually have two immisciblechains), such molecules self-assemble to form lamellar, hexagonal, micellar cubic and bicontinuous cubic structures. However, the presence of the third immiscible chain significantly increases structural complexity and hierarchical ordering can occur.
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    Natural ageing behaviour in Al-Cu alloys containing Sc and Z
    (Australian Nuclear Science and Technology Organisation, 2021-11-24) Jiang, L; Wood, K; Knott, RB; Sokolova, AV; Dorin, T
    The 2xxx series Al-Cu alloys have been extensively used as engineering structures and components of lightweight vehicles due to their excellent strength-to-weight ratio. Recent research has demonstrated that further substantial enhancement in the strength of Al-Cu alloys could be achieved by adding Sc and Zr by forming nano-sized Al3(Sc, Zr) dispersoids. However, further development and manufacturing of these new Sc and Zr-containing Al-Cu alloys are limited by a lack of basic understanding of the effect of Al3(Sc, Zr) dispersoids on the microstructural evolution during room temperature storage after quenching from solution treatment (called natural ageing). In this work, therefore, we have studied the effect of Al3(Sc, Zr) dispersoids on natural ageing behaviour in an Al-4wt.%Cu-0.1wt.%Sc-0.1wt.%Zr alloy using small-angle neutron and x-ray scattering (SANS and SAXS). The hardness measurement shows that the presence of Al3(Sc, Zr) dispersoids significantly delays the natural ageing kinetics of Al-Cu alloys. SANS was used to quantify the size distribution of Al3(Sc, Zr) dispersoids which is ~ 25 ± 3 nm. In-situ SAXS results show that the presence of Al3(Sc, Zr) dispersoids results in a significant delay in the solute clustering formation during natural ageing. This is attributed to the suppression of the natural ageing kinetics in the Al-Cu-Sc-Zr alloys. These results were confirmed by differential scanning calorimetry (DSC) and high resolution transmission electron microscopy (TEM). The suppression mechanism is hypothesized to come from the dispersoids and Sc solute acting as vacancy sinks which slows down the diffusion of solute at room temperatures. © 2021 The Authors
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    Samurai’s swords, a non-invasive investigation by neutron techniques
    (Scientific.Net, 2020-03-01) Salvemini, F; Luzin, V; Avdeev, M; Tremsin, AS; Sokolova, AV; Gregg, AWT; Wensrich, CM; Gatenby, S; Kim, MJ; Grazzi, F
    A synergic combination of neutron techniques was applied to characterize non-invasively the laminated structure of a set of ancient katana, part of the East Asian Collection of the Museum of Applied Arts and Sciences (MAAS) in Sydney. Neutron tomography, diffraction, residual stress and Bragg-edge transmission analyses were undertaken on samples of well-known origin, time period and authorship to create a reference database on the main manufacturing methods developed by Japanese swordsmiths. In the attempt to attribute mumei (no-signature) blades basing on a scientific analytical method rather than a stylistic analysis, data from the reference samples were benchmarked against the results obtained from the unknown blade to identify differences and commonalities in the production process. © 2020 by Trans Tech Publications Ltd.
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    SANS time-of-flight instrument Bilby at ACNS, ANSTO
    (Australian Institute of Nuclear Science and Engineering (AINSE), 2020-11-11) Sokolova, AV; Whitten, AE; de Campo, L
    ANSTO for more than ten years successfully operates Small Angle Neutron Scattering (SANS) instrument Quokka [1] and in 2016 commenced user operation of the second SANS instrument, Bilby [2]. Ultra-small angle scattering machine Kookaburra [3] is completing the set of the SANS instruments at ANSTO. Bilby exploits neutron Time-of-Flight (ToF) to extend the measurable Q-range, over and above what is possible on a conventional reactor-based monochromatic SANS instrument. In ToF mode, the choppers are used to create neutron pulses of variable (~3% ‒ 30%) wavelength resolution. Two arrays of position-sensitive detectors in combination with utilizing of wide wavelength range provide the capability to collect scattering data of wide angular diapason without changing the experimental set-up (maximum accessible Q on the instrument is 0.001-1.8Å-1). Additionally to the ToF, Bilby can operate in monochromatic mode. The question is how the advanced design features can be applied to the real scientific questions. In short, having a large dynamic range available in one go opens up a possibility to study complex systems like micelles and hierarchical materials. Additionally, there is a range of sample environments available allowing to change conditions in situ, which is priceless for study a range of samples stretching from colloids to metals. In my presentation, I will be giving several examples demonstrating how ToF SANS can bring light to structural changes of the surfactant wormlike micelles structure under various conditions. Some cases will be presented to show that the monochromatic mode is also the one producing valuable results. The main accent will be made on a recently published work, done solely on Bilby along with examples of combining SANS and USANS techniques. © The authors.
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    Small angle neutron scattering capability at ANSTO
    (Australian Nuclear Science and Technology Organisation, 2021-11-24) de Campo, L; Elliott, EP; Knott, RB; Mata, JP; Sokolova, AV; Whitten, AE; Wood, K; Wu, CM
    The ANSTO Lucas Heights campus is home to three world-class small angle neutron scattering (SANS) instruments: Bilby, a time-of-flight SANS instrument [1], Kookaburra, an Ultra-Small Angle Neutron scattering instrument [2] and Quokka, a monochromatic SANS instrument [3]. Together they cover the structure of materials from 1 nm to > 20 microns. As well as recent scientific highlights, we here outline the updates from the group since the last ANSTO user meeting, notably: - The replacement of our lab-based small angle X-ray instrument with a state-of-the-art instrument along with a range of dedicated sample environments, currently being procured and due for installation early 2022. - The new rheometer for in-situ measurements on the three neutron instruments. - Our recently developed GiSANS setup, funded by the National Synchrotron Radiation Research Center. © The Authors
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    Small angle scattering: instrumentation and applications to study various materials at the nanoscale
    (Australian Institute of Physics, 2011-02-03) Sokolova, AV
    Small Angle Scattering (SAS) technique is a powerful unique tool to study various materials. The method provides structural information on condensed phases of different nature at resolution level ranging from about 1 to about hundreds of nanometers. Both, X-rays and neutrons can be utilized in SAS method. Number of large facilities provides access to SAS X-rays (SAXS) and neutron (SANS) instruments. Australian Nuclear Science and technology Organization (ANSTO, Sydney, Australia) successfully operates one SANS instrument Quokka and recently commenced construction of the second SANS instrument, Bilby. The presentation will be focused on possibilities to use SAS neutron technique in applied science, in particular in biotechnology and medicine, in metal and in magnetic devices industry. The advantages and limitations of the method will be underlined. The requirements to samples preparation will be listed. The capabilities of two instruments at ANSTO, Quokka and Bilby as well as a way to get access for use of the instruments will be described
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    Small-angle x-ray scattering study of the effect of pH and salts on 11S soy glycinin in the freeze-dried powder and solution states
    (American Chemical Society, 2010-01-27) Sokolova, AV; Kealley, CS; Hanley, TL; Rekas, A; Gilbert, EP
    The nanostructures from powders of native protein, glycinin, and corresponding solutions from which the powders have been formed, have been studied as a function of pH and 1 M salts using small-angle X-ray scattering. All powders showed Porod scattering with the exception of that prepared from the solution close to pl which displayed fractal behavior. Well-defined Bragg peaks in the powder scattering at pH 5, pH 7, and 1 M NaCl indicate the presence of long-range order. The scattering from solutions at pH 7, pH 9, and 1 M NaCl can be described well on the basis of particles derived from the known atomic structures of homohexameric glycinin. Extreme acidic (pH 2) and basic (pH 11) environments lead to the partial denaturation of glycinin. Decreasing the pH to 2 initiates dissociation of the hexameric structure, while increasing the pH to 11, as well as the presence of 1 M NaSCN, results in the formation of large unimodal particles. This is reflected by "featureless" SAXS patterns for both powders and solutions. © 2010, American Chemical Society
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    Structural characterization by small angle scattering suggests models for monomeric and dimeric forms of full-length ezrin
    (Australian Institute of Nuclear Science and Engineering, 2016-11-29) Phang, JM; Harrop, SJ; Duff, AP; Sokolova, AV; Crossett, B; Walsh, JC; Beckham, SA; Nguyen, CD; Davies, RB; Glöckner, C; Bromley, EH; Wilk, KE; Curmi, PM
    Ezrin is member of the ERM (Ezrin-Radixin-Moesin) family of proteins that have been conserved through metazoan evolution. These proteins have dormant and active forms, there the latter links the actin cytoskeleton to membranes. ERM proteins have three domains: an N-terminal FERM (band Four-point-one ERM) domain comprising three subdomains (F1, F2 and F3); a helical domain; and a C-terminal actin-binding domain. In the dormant form, FERM and C-terminal domains form a stable complex. We have determined crystal structures of the active FERM domain and the dormant FERM:C-terminal domain complex of human ezrin. We observe bistable array of phenylalanine residues in the core of subdomain F3 that is mobile in the active form and locked in the dormant form. As subdomain F3 is pivotal in binding membrane proteins and phospholipids, these transitions may facilitate activation and signaling. Full-length ezrin forms stable monomers and dimers. We used small-angle x-ray scattering to determine the solution structures of these species. As expected, the monomer shows a globular domain with a protruding helical coiled-coil. The dimer shows an elongated dumbbell structure that is twice as long as the monomer. By aligning ERM sequences spanning metazoan evolution, we show that the central helical region is conserved, preserving the heptad repeat. Using this, we have built a dimer model where each monomer forms half of an elongated anti-parallel coiled-coil with domain swapped FERM:C-terminal domain complexes at each end. The model suggests that ERM dimers may bind to actin in a parallel fashion.
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    Structural features of fab fragments of rheumatoid factor IgM-RF in solution
    (Springer, 2008-05) Volkov, VV; Lapuk, VA; Shtykova, EV; Stepina, ND; Dembo, KA; Sokolova, AV; Amarantov, SV; Timofeev, VP; Ziganshin, RK; Varlamova, EY
    The structural features of the Fab fragments of monoclonal (Waldenstrom's disease) immunoglobulin M (I-M) and rheumatoid immunoglobulin M (lgM-RF) were studied by a complex of methods, including small-angle X-ray scattering (SAXS), electron spin resonance (ESR), and mass spectrometry (MS). The Fab-RF fragment was demonstrated to be much more flexible in the region of interdomain contacts, the molecular weights and the shapes of the Fab and Fab-RF macromolecules in solution being only slightly different. According to the ESR data, the rotational correlation time for a spin label introduced into the peptide sequence for Fab is twice as large as that for Fab-RF (21 +/- 2 and 11 +/- 1 ns, respectively), whereas the molecular weights of these fragments differ by only 0.5% (mass-spectrometric data), which correlates with the results of molecular-shape modeling by small-angle X-ray scattering. The conclusion about the higher flexibility of the Fab-RF fragment contributes to an understanding of the specificity of interactions between the rheumatoid factor and the anti-ens of the own organism. © 2008, Springer.
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    Structure of dopamine induced α-synuclein oligomers
    (Springer, 2010-3-23) Rekas, A; Knott, RB; Sokolova, AV; Barnham, KJ; Perez, KA; Masters, CL; Drew, SC; Cappai, R; Curtain, CC; Pham, CLL
    Inclusions of aggregated α-synuclein (α-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson’s disease (PD). In vitro, α-syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non-amyloidogenic oligomers. We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS) and circular dichroism spectroscopy to study the characteristics of α-syn oligomers formed in the presence of DA. Our SAXS data show that the trimers formed by the action of DA on α-syn consist of overlapping worm-like monomers, with no end-to-end associations. This lack of structure contrasts with the well-established, extensive β-sheet structure of the amyloid fibril form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the four methionine residues at the C- and N-terminal ends of α-syn molecules prevents their end-to-end association and stabilises oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting formation of the β-sheet structure found in other pre-fibrillar forms of α-syn. © 2010, Springer.