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https://www.readbyqxmd.com/read/28102321/the-chaperonin-cct-inhibits-assembly-of-%C3%AE-synuclein-amyloid-fibrils-by-a-specific-conformation-dependent-interaction
#1
Begoña Sot, Alejandra Rubio-Muñoz, Ahudrey Leal-Quintero, Javier Martínez-Sabando, Miguel Marcilla, Cintia Roodveldt, José M Valpuesta
The eukaryotic chaperonin CCT (chaperonin containing TCP-1) uses cavities built into its double-ring structure to encapsulate and to assist folding of a large subset of proteins. CCT can inhibit amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington's disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of α-synuclein A53T, one of the mutants responsible for Parkinson's disease...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102308/corrigendum-pre-amyloid-oligomers-budding-a-metastatic-mechanism-of-proteotoxicity
#2
Fabrizio Bernini, Daniele Malferrari, Marcello Pignataro, Carlo Augusto Bortolotti, Giulia Di Rocco, Lidia Lancellotti, Maria Franca Brigatti, Rakez Kayed, Marco Borsari, Federica Del Monte, Elena Castellini
No abstract text is available yet for this article.
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102201/direct-pip2-binding-mediates-stable-oligomer-formation-of-the-serotonin-transporter
#3
Andreas Anderluh, Tina Hofmaier, Enrico Klotzsch, Oliver Kudlacek, Thomas Stockner, Harald H Sitte, Gerhard J Schütz
The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102071/temperature-induced-misfolding-in-prion-protein-evidences-of-multiple-partially-disordered-states-stabilized-by-non-native-hydrogen-bonds
#4
Neharika G Chamachi, Suman Chakrabarty
The structural basis of misfolding pathways of a cellular Prion (PrP(C)) into the toxic scrapie form (PrP(SC)) and identification of possible intermediates (e.g. PrP(*)) still eludes us. In this work, we have used a cumulative ~65µs of Replica Exchange Molecular Dynamics simulation data to construct the conformational free energy landscapes and capture the structural and thermodynamic characteristics associated with various stages of the thermal denaturation process in human Prion protein. The temperature dependent free energy surfaces consist of multiple metastable states stabilized by non-native contacts and hydrogen bonds, thus rendering the protein prone towards misfolding...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28101869/fibrin-formation-structure-and-properties
#5
John W Weisel, Rustem I Litvinov
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28098463/absolute-configuration-of-native-oligomeric-proanthocyanidins-with-dentin-biomodification-potency
#6
Joo-Won Nam, Rasika S Phansalkar, David C Lankin, James B McAlpine, Ariene A Leme-Kraus, Cristina M P Vidal, Li-She Gan, Ana Bedran-Russo, Shao-Nong Chen, Guido F Pauli
The structurally complex oligomeric proanthocyanidins (OPACs) are promising biomimetic agents, capable of strengthening the macromolecular backbone of teeth via intermolecular and intermicrofibrillar cross-linking. This study establishes analytical methods capable of determining the absolute configuration of the catechin-type monomeric units of underivatized OPACs. This preserves the capacity of their biological evaluation, aimed at understanding the inevitably stereospecific interactions between the OPACs and dentin collagen...
January 18, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28098204/strain-specific-fibril-propagation-by-an-a%C3%AE-dodecamer
#7
Dexter N Dean, Pradipta K Das, Pratip Rana, Franklin Burg, Yona Levites, Sarah E Morgan, Preetam Ghosh, Vijayaraghavan Rangachari
Low molecular weight oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents in the etiology of Alzheimer disease (AD). Polymorphism observed within the aggregation end products of fibrils are known to arise due to microstructural differences among the oligomers. Diversity in aggregate morphology correlates with the differences in AD, cementing the idea that conformational strains of oligomers could be significant in phenotypic outcomes. Therefore, it is imperative to determine the ability of strains to faithfully propagate their structure...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097276/hydrophobicity-determines-the-fate-of-self-assembled-fluorescent-nanoparticles-in-cells
#8
Arthur H A M van Onzen, Lorenzo Albertazzi, Albertus P H J Schenning, Lech-Gustav Milroy, Luc Brunsveld
The fate of small molecule nanoparticles (SMNPs) composed of self-assembling intrinsically fluorescent π-conjugated oligomers was studied in cells as a function of side-chain hydrophobicity. While the hydrophobic SMNPs remained intact upon cellular uptake, the more hydrophilic SMNPs disassembled and dispersed throughout the cytosol.
January 18, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28096453/programmable-formation-of-catalytic-rna-triangles-and-squares-by-assembling-modular-rna-enzymes
#9
Hiroki Oi, Daisuke Fujita, Yuki Suzuki, Hiroshi Sugiyama, Masayuki Endo, Shigeyoshi Matsumura, Yoshiya Ikawa
RNA is a biopolymer that is attractive for constructing nanoscale objects with complex structures. Three-dimensional (3D) structures of naturally occurring RNAs often have modular architectures. The 3D structure of a group I (GI) ribozyme from Tetrahymena has a typical modular architecture, which can be separated into two structural modules (ΔP5 and P5abc). The fully active ribozyme can be reconstructed by assembling the two separately prepared modules through highly specific and strong assembly between ΔP5 ribozyme and P5abc RNA...
January 17, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28096355/a-natural-product-inhibits-the-initiation-of-%C3%AE-synuclein-aggregation-and-suppresses-its-toxicity
#10
Michele Perni, Céline Galvagnion, Alexander Maltsev, Georg Meisl, Martin B D Müller, Pavan K Challa, Julius B Kirkegaard, Patrick Flagmeier, Samuel I A Cohen, Roberta Cascella, Serene W Chen, Ryan Limboker, Pietro Sormanni, Gabriella T Heller, Francesco A Aprile, Nunilo Cremades, Cristina Cecchi, Fabrizio Chiti, Ellen A A Nollen, Tuomas P J Knowles, Michele Vendruscolo, Adriaan Bax, Michael Zasloff, Christopher M Dobson
The self-assembly of α-synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096191/allosteric-modulation-of-the-substrate-specificity-of-acyl-coa-wax-alcohol-acyltransferase-2-awat2
#11
Jason M Arne, Made Airanthi K Widjaja-Adhi, Taylor Hughes, Kevin W Huynh, Josie A Silvaroli, Sylwia Chelstowska, Vera Y Moiseenkova-Bell, Marcin Golczak
The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of readily available pool of cis retinoids in the eye...
January 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28094516/designed-dna-crystal-habit-modifiers
#12
Diana Zhang, Paul J Paukstelis
DNA is now one of the most widely used molecules for programmed self-assembly of discrete nanostructures. One of the long-standing goals of the DNA nanotechnology field has been the assembly of periodic, macroscopic 3D DNA crystals for controlled positioning of guest molecules to be used in a variety of applications. With continuing successes in assembling DNA crystals there is an enhanced need to tailor macroscopic crystal properties - including morphology - to enable their integration into more complex systems...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28094495/bacoside-a-an-indian-traditional-medicine-substance-inhibits-beta-amyloid-cytotoxicity-fibrillation-and-membrane-interactions
#13
Ravit Malishev, Shira Shaham-Niv, Sukhendu Nandi, Sofiya Kolusheva, Ehud Gazit, Raz Jelinek
Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, pre-incubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles...
January 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28094360/impact-of-morphology-on-polaron-delocalization-in-a-semicrystalline-conjugated-polymer
#14
Robert Steyrleuthner, Yuexing Zhang, Lei Zhang, Felix Kraffert, Benjamin P Cherniawski, Robert Bittl, Alejandro L Briseno, Jean-Luc Bredas, Jan Behrends
We investigate the delocalization of holes in the semicrystalline conjugated polymer poly(2,5-bis(3-alkylthiophene-2-yl)thieno[3,2-b]thiophene) (PBTTT) by directly measuring the hyperfine coupling between photogenerated polarons and bound nuclear spins using electron nuclear double resonance spectroscopy. An extrapolation of the corresponding oligomer spectra reveals that charges tend to delocalize over 4.0-4.8 nm with delocalization strongly dependent on molecular order and crystallinity of the PBTTT polymer thin films...
January 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28093972/conformation-as-the-therapeutic-target-for-neurodegenerative-diseases
#15
Rajaraman Krishnan, Franz Hefti, Haim Tsubery, Michal Lulu, Ming Proschitsky, Richard Fisher
Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets...
January 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28092632/the-tilt-dependent-potential-of-mean-force-of-a-pair-of-dna-oligomers-from-all-atom-molecular-dynamics-simulations
#16
Ruggero Cortini, Xiaolin Cheng, Jeremy C Smith
Electrostatic interactions between DNA molecules have been extensively studied experimentally and theoretically, but several aspects (e.g. its role in determining the pitch of the cholesteric DNA phase) still remain unclear. Here, we performed large-scale all-atom molecular dynamics simulations in explicit water and 150 mM sodium chloride, to reconstruct the potential of mean force (PMF) of two DNA oligomers 24 base pairs long as a function of their interaxial angle and intermolecular distance. We find that the potential of mean force is dominated by total DNA charge, and not by the helical geometry of its charged groups...
January 16, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28091636/assessing-the-electrochemical-properties-of-polypyridine-and-polythiophene-for-prospective-applications-in-sustainable-organic-batteries
#17
Rafael B Araujo, Amitava Banerjee, Puspamitra Panigrahi, Li Yang, Martin Sjödin, Maria Strømme, C Moyses Araujo, Rajeev Ahuja
Conducting polymers are being considered promising candidates for sustainable organic batteries mainly due to their fast electron transport properties and high recyclability. In this work, the key properties of polythiophene and polypyridine have been assessed through a combined theoretical and experimental study focusing on such applications. A theoretical protocol has been developed to calculate redox potentials in solution within the framework of the density functional theory and using continuous solvation models...
January 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28091541/apelin-receptor-homodimer-oligomers-revealed-by-single-molecule-imaging-and-novel-g-protein-dependent-signaling
#18
Xin Cai, Bo Bai, Rumin Zhang, Chunmei Wang, Jing Chen
The apelin receptor (APJ) belongs to family A of the G protein-coupled receptors (GPCRs) and is a potential pharmacotherapeutic target for heart failure, hypertension, and other cardiovascular diseases. There is evidence APJ heterodimerizes with other GPCRs; however, the existence of APJ homodimers and oligomers remains to be investigated. Here, we measured APJ monomer-homodimer-oligomer interconversion by monitoring APJ dynamically on cells and compared their proportions, spatial arrangement, and mobility using total internal reflection fluorescence microscopy, resonance energy transfer, and proximity biotinylation...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090689/%C3%AE-aminoxy-peptoids-a-unique-peptoid-backbone-with-a-preference-for-cis-amide-bonds
#19
Viktoria Krieger, Emanuele Ciglia, Roland Thoma, Vera Vasylyeva, Benedikt Frieg, Nader de Sousa Amadeu, Thomas Kurz, Christoph Janiak, Holger Gohlke, Finn Kristian Hansen
α-Peptoids, or N-substituted glycine oligomers, are an important class of peptidomimetic foldamers with proteolytic stability. Nevertheless, the presence of cis-/trans-amide bond conformers, which contribute to the high flexibility of α-peptoids, is considered as a major drawback. A modified peptoid backbone with an improved control of the amide bond geometry could therefore help to overcome this limitation. Here we have performed the first thorough analysis of the folding propensities of α-aminoxy peptoids (or N-substituted 2-aminoxyacetic acid oligomers)...
January 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#20
Pietro Giusti, Stephen D Skaper, Laura Facci, Morena Zusso
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
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