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https://www.readbyqxmd.com/read/28104892/mechanistic-basis-for-a-molecular-triage-reaction
#1
Sichen Shao, Monica C Rodrigo-Brenni, Maryann H Kivlen, Ramanujan S Hegde
Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28103900/gde2-is-essential-for-neuronal-survival-in-the-postnatal-mammalian-spinal-cord
#2
Clinton Cave, Sungjin Park, Marianeli Rodriguez, Mai Nakamura, Ahmet Hoke, Mikhail Pletnikov, Shanthini Sockanathan
BACKGROUND: Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2's roles beyond embryonic neurogenesis have yet to be defined. METHOD: Using a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 (-/-) mouse for evidence of degenerative neuropathology...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28100778/structure-of-the-z-ring-associated-protein-zapd-bound-to-the-c-terminal-domain-of-the-tubulin-like-protein-ftsz-suggests-mechanism-of-z-ring-stabilization-through-ftsz-crosslinking
#3
Maria Schumacher, Kuo-Hsiang Huang, Wenjie Zeng, Anuradha Janakiraman
Cell division in most bacteria is mediated by the tubulin-like FtsZ protein, which polymerizes in a GTP-dependent manner to form the cytokinetic Z ring. A diverse repertoire of FtsZ binding proteins affect FtsZ localization and polymerization to ensure correct Z ring formation. Many of these proteins bind the C-terminal domain (CTD) of FtsZ, which serves as a hub for FtsZ regulation. FtsZ ring-associated proteins, ZapA-D (Zaps), are important FtsZ regulatory proteins that stabilize FtsZ assembly and enhance Z ring formation by increasing lateral assembly of FtsZ protofilaments, which then form the Z ring...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100189/an-snp-based-saturated-genetic-map-and-qtl-analysis-of-fruit-related-traits-in-zucchini-using-genotyping-by-sequencing
#4
Javier Montero-Pau, José Blanca, Cristina Esteras, Eva Ma Martínez-Pérez, Pedro Gómez, Antonio J Monforte, Joaquín Cañizares, Belén Picó
BACKGROUND: Cucurbita pepo is a cucurbit with growing economic importance worldwide. Zucchini morphotype is the most important within this highly variable species. Recently, transcriptome and Simple Sequence Repeat (SSR)- and Single Nucleotide Polymorphism (SNP)-based medium density maps have been reported, however further genomic tools are needed for efficient molecular breeding in the species. Our objective is to combine currently available complete transcriptomes and the Zucchini genome sequence with high throughput genotyping methods, mapping population development and extensive phenotyping to facilitate the advance of genomic research in this species...
January 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28097911/design-synthesis-and-docking-study-of-novel-coumarin-ligands-as-potential-selective-acetylcholinesterase-inhibitors
#5
Fatih Sonmez, Belma Zengin Kurt, Isil Gazioglu, Livia Basile, Aydan Dag, Valentina Cappello, Tiziana Ginex, Mustafa Kucukislamoglu, Salvatore Guccione
New coumaryl-thiazole derivatives with the acetamide moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and in vitro tested as acetylcholinesterase (AChE) inhibitors. 2-(diethylamino)-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)acetamide (6c, IC50 value of 43 nM) was the best AChE inhibitor with a selectivity index of 4151.16 over BuChE. Kinetic study of AChE inhibition revealed that 6c was a mixed-type inhibitor. Moreover, the result of H4IIE hepatoma cell toxicity assay for 6c showed negligible cell death...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28090783/probing-the-druggability-of-membrane-bound-rab5-by-molecular-dynamics-simulations
#6
Eileen Edler, Matthias Stein
Rab5 is a small GTPase and a key regulator in early endosomal trafficking. Rab5 and its effectors are involved in a large number of infectious diseases and certain types of cancer. We performed µs atomistic molecular dynamics simulations of inactive and active full-length Rab5 anchored to a complex model bilayer with composition of the early endosome membrane. Direct interactions between the Rab5 G domain and the bilayer were observed. We found two dominant nucleotide-dependent orientations characterised by a different accessibility of the switch regions...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28088448/fast-formation-of-low-defect-density-tethered-bilayers-by-fusion-of-multilamellar-vesicles
#7
Tadas Ragaliauskas, Mindaugas Mickevicius, Bozena Rakovska, Tadas Penkauskas, David J Vanderah, Frank Heinrich, Gintaras Valincius
A facile and reproducible preparation of surface-supported lipid bilayers is essential for fundamental membrane research and biotechnological applications. We demonstrate that multilamellar vesicles fuse to molecular-anchor-grafted surfaces yielding low-defect-density, tethered bilayer membranes. Continuous bilayers are formed within 10min, while the electrically insulating bilayers with <0.1μm(-2) defect density can be accomplished within 60min. Surface plasmon resonance spectroscopy indicates that an amount of lipid material transferred from vesicles to a surface is inversely proportional to the density of an anchor, while the total amount of lipid that includes tethered and transferred lipid remains constant within 5% standard error...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28077875/structural-basis-of-co-translational-quality-control-by-arfa-and-rf2-bound-to-ribosome
#8
Fuxing Zeng, Yanbo Chen, Jonathan Remis, Mrinal Shekhar, James C Phillips, Emad Tajkhorshid, Hong Jin
Quality control mechanisms intervene appropriately when defective translation events occur, in order to preserve the integrity of protein synthesis. Rescue of ribosomes translating on messenger RNAs that lack stop codons is one of the co-translational quality control pathways. In many bacteria, ArfA recognizes stalled ribosomes and recruits the release factor RF2, which catalyses the termination of protein synthesis. Although an induced-fit mechanism of nonstop mRNA surveillance mediated by ArfA and RF2 has been reported, the molecular interaction between ArfA and RF2 in the ribosome that is responsible for the mechanism is unknown...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28075501/a-recoverable-ruthenium-aqua-complex-supported-onto-silica-particles-an-efficient-epoxidation-catalyst
#9
M Isabel Romero, Ingrid Ferrer, Xavier Fontrodona, Anna Roig, Montserrat Rodríguez
The preparation and characterization of new complexes with a phosphonated trpy ligand (trpy-P-Et) and a bidentate pyridylpyrazole (pypz-Me) ligand, with formula [RuII(trpy-P-Et)(pypz-Me)X]n+ (X = Cl, n= 1, 2; X=H2O, n=2, 3) is described, together with the anchoring of 3 onto two types of supports: mesoporous silica particles (SP) and silica coated magnetic particles (MSP). The aqua complex 3 is easily obtained through reflux of 2 in water and displays a bielectronic Ru(IV/II) redox process. It has been anchored onto SP and MSP supports through two different synthetic strategies, yielding the heterogeneous systems SP@3 and MSP@3 that have been fully characterized by IR, UV-vis, SEM, CV and DPV...
January 11, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28075131/classical-galactosemia-insight-into-molecular-pathomechanisms-by-differential-membrane-proteomics-of-fibroblasts-under-galactose-stress
#10
Simon Staubach, Stefan Müller, Murat Pekmez, Franz-Georg Hanisch
Classical galactosemia, a hereditary metabolic disease caused by the deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), results in an impaired galactose metabolism and serious long-term developmental affection of the CNS and ovaries, potentially related in part to endogenous galactose-induced protein dysglycosylation. In search for galactose-induced changes in membrane raft proteomes of GALT-deficient cells, we performed differential analyses of lipid rafts from patient-derived (Q) and sex- and age-matched control fibroblasts (H) in the presence or absence of the stressor...
January 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28075125/multifunctional-nanoparticles-by-coordinative-self-assembly-of-his-tagged-units-with-metal-organic-frameworks
#11
Ruth Röder, Tobias Preiß, Patrick Hirschle, Benjamin Steinborn, Andreas Zimpel, Miriam Hoehn, Joachim O Rädler, Thomas Bein, Ernst Wagner, Stefan Wuttke, Ulrich Lächelt
Self-assembly of individual units into multicomponent complexes is a powerful approach for the generation of functional super-structures. We present the coordinative interaction of oligohistidine-tags (His-tags) with metal-organic framework nanoparticles (MOF NPs). By this novel concept, different molecular units can be anchored on the outer surface of MOF NPs in a self-assembly process generating multifunctional nanosystems. The article focuses on two main objectives: first, the detailed investigation of the assembly process and fundamental establishment of the novel functionalization concept; and second, its subsequent use for the development of biomacromolecule (e...
January 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28073939/nanoscale-molecular-reorganization-of-the-inhibitory-postsynaptic-density-is-a-determinant-of-gabaergic-synaptic-potentiation
#12
Francesca Pennacchietti, Sebastiano Vascon, Thierry Nieus, Christian Rosillo, Sabyasachi Das, Shiva Tyagarajan, Alberto Diaspro, Alessio Del Bue, Enrica Maria Petrini, Andrea Barberis, Francesca Cella Zanacchi
: Gephyrin is a key scaffold protein mediating the anchoring of GABAA receptors at inhibitory synapses. Here we exploited super-resolution techniques combined with proximity-based clustering analysis and model simulations to investigate the single molecule gephyrin reorganization during plasticity of inhibitory synapses in mouse hippocampal cultured neurons. This approach revealed that during the expression of inhibitory long-term potentiation the increase of gephyrin density at postsynaptic sites is associated with the promoted formation of gephyrin nano-domains...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073270/cooperative-molecular-behavior-enhances-the-thermal-conductance-of-binary-self-assembled-monolayer-junctions
#13
Shubhaditya Majumdar, Jonathan A Malen, Alan J H McGaughey
The effect of the local molecular environment on thermal transport through organic-inorganic heterojunctions is investigated using binary self-assembled monolayer (SAM) junctions built from a mixture of alkanethiol and alkanedithiol species sandwiched between gold leads. Thermoreflectance measurements and molecular dynamics simulations demonstrate that the thermal conductances of the binary SAM junctions vary with molecular composition and are greater than predictions of a parallel resistance model. The enhancement results from increased thermal transport through the alkanethiols, whose terminal methyl groups are confined by the anchored alkanedithiols...
January 11, 2017: Nano Letters
https://www.readbyqxmd.com/read/28070969/sensitizers-for-aqueous-based-solar-cells
#14
Chun-Ting Li, Ryan Yeh-Yung Lin, Jiann T Lin
Aqueous dye-sensitized solar cells (DSSCs) are attractive due to sustainability and safety of using water as the solvent of the redox mediators, and possible applications of photoelectrochemical water splitting. However, higher tendency of dye-leaching by water and lower wettability of dye molecules are two major obstacles need to be tackled for future applications of aqueous DSSCs. Sensitizers designed for aqueous DSSCs are discussed based on their functions, such as modification of the molecular skeleton and the anchoring group for better stability against dye-leaching by water, and incorporation of hydrophilic entity in the dye molecule or addition of surfactant to the system to increase wettability of the dye for more facile dye regeneration...
January 10, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28070066/molecular-structural-analysis-of-spider-s-capture-thread-and-viscid-droplets-studied-by-microscopic-ft-ir-spectroscopy
#15
Hironobu Yabe, Norihisa Katayama, Mitsuhiro Miyazawa
The molecular structural analysis of capture thread, including its viscid droplets of oriental golden orb-web spider Nephila clavata, has been performed by microscopic FT-IR spectroscopy. The obtained spectra of capture threads with and without viscid droplets indicate that the features in the region of 1400 - 1000 cm(-1) will be useful as marker bands for the degree of the dissolving of viscid droplet; further, the bands at 1395 and 1335 cm(-1) are attributable to the components of anchoring granules located at the inner side of viscid droplets...
2017: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/28069669/refining-the-molecular-organization-of-the-cardiac-intercalated-disc
#16
REVIEW
Sarah H Vermij, Hugues Abriel, Toon A B van Veen
This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and desmosomes function as cell anchors and connect intermediate filaments. Furthermore, ion channels reside in the ID. Mutations in ID proteins have been associated with cardiac arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy...
January 8, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28069508/bio-inspired-virus-imprinted-polymer-for-prevention-of-viral-infections
#17
Ning Li, Yan-Jie Liu, Fei Liu, Mi-Fang Luo, Ying-Chun Wan, Zheng Huang, Qiang Liao, Fang-Sheng Mei, Zhi-Cheng Wang, Ai-Yin Jin, Yun Shi, Bin Lu
: A novel virus-imprinted polymer for prevention of viral infection was prepared by anchoring molecularly imprinted polymer (MIP) on the surface of poly-dopamine (PDA)-coated silica particles. The imprinting reaction was carried out via self-polymerization of dopamine in the presence of a virus template. Plaque forming assay indicated that the MIP exhibited selective anti-viral infection properties for the template virus in complex media containing different interfering substances, and even other types of viruses...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28068766/membrane-adhesion-through-bridging-by-multimeric-ligands
#18
Omar Alexander Amjad, Bortolo Matteo Mognetti, Pietro Cicuta, Lorenzo Di Michele
Ligand/receptor multivalent interactions have been exploited to drive the self-assembly of nanoparticles, hard colloids, and more recently compliant units including emulsion droplets and lipid vesicles. In deformable liposomes, the formation of links between two membranes produces morphological changes depending on the amount of ligands in the environment. Here we study a proof-of-concept biosensing system in which single lipid vesicles adhere to a flat supported lipid bilayer, both decorated with membrane-anchored biotinylated receptors...
January 10, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28068761/the-orbital-selection-rule-for-molecular-conductance-as-manifested-in-tetraphenyl-based-molecular-junctions
#19
Marius Bürkle, Limin Xiang, Guangfeng Li, Ali Rostamian, Thomas Hines, Shaoyin Guo, Gang Zhou, Nongjian Tao, Yoshihiro Asai
Using two tetraphenylbenzene isomers differing only by the anchoring points to the gold electrodes, we investigate the influence of quantum interference on the single molecule charge transport. The distinct anchor points are realized by selective halogen-mediated binding to the electrodes by formation of surface-stabilized isomers after iodine cleavage. Both isomers are essentially chemically identical and only weakly perturbed by the electrodes avoiding largely parasitic effects, which allows us to focus solely on the relation between quantum interference and the intrinsic molecular properties...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28068080/effect-of-the-southeast-asian-ovalocytosis-deletion-on-the-conformational-dynamics-of-the-signal-anchor-transmembrane-segment-1-of-the-red-cell-anion-exchanger-1-ae1-band-3-slc4a1
#20
Philip W Fowler, Mark S P Sansom, Reinhart A F Reithmeier
The first transmembrane (TM1) helix in the red cell anion exchanger (AE1, Band 3, SLC4A1) acts as an internal signal anchor that binds the signal recognition particle and directs the nascent polypeptide chain to the endoplasmic reticulum (ER) membrane where it moves from the translocon laterally into the lipid bilayer. The sequence N-terminal to TM1 forms an amphipathic helix that lies at the membrane interface connected to TM1 by a bend at Pro403. Southeast Asian Ovalocytosis (SAO) is a red cell abnormality caused by a nine-amino acid deletion (Ala400-Ala408) at the N-terminus of TM1...
January 9, 2017: Biochemistry
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