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https://www.readbyqxmd.com/read/28538729/cryo-em-structure-of-the-activated-glp-1-receptor-in-complex-with-a-g-protein
#1
Yan Zhang, Bingfa Sun, Dan Feng, Hongli Hu, Matthew Chu, Qianhui Qu, Jeffrey T Tarrasch, Shane Li, Tong Sun Kobilka, Brian K Kobilka, Georgios Skiniotis
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538153/new-continuum-approaches-for-determining-protein-induced-membrane-deformations
#2
David Argudo, Neville P Bethel, Frank V Marcoline, Charles W Wolgemuth, Michael Grabe
The influence of the membrane on transmembrane proteins is central to a number of biological phenomena, notably the gating of stretch activated ion channels. Conversely, membrane proteins can influence the bilayer, leading to the stabilization of particular membrane shapes, topological changes that occur during vesicle fission and fusion, and shape-dependent protein aggregation. Continuum elastic models of the membrane have been widely used to study protein-membrane interactions. These mathematical approaches produce physically interpretable membrane shapes, energy estimates for the cost of deformation, and a snapshot of the equilibrium configuration...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538145/nmr-analysis-of-amide-hydrogen-exchange-rates-in-a-pentapeptide-repeat-protein-from-a-%C3%A2-thaliana
#3
Shenyuan Xu, Shuisong Ni, Michael A Kennedy
At2g44920 from Arabidopsis thaliana is a pentapeptide-repeat protein (PRP) composed of 25 repeats capped by N- and C-terminal α-helices. PRP structures are dominated by four-sided right-handed β-helices typically consisting of mixtures of type II and type IV β-turns. PRPs adopt repeated five-residue (Rfr) folds with an Rfr consensus sequence (STAV)(D/N)(L/F)(S/T/R)(X). Unlike other PRPs, At2g44920 consists exclusively of type II β-turns. At2g44920 is predicted to be located in the thylakoid lumen although its biochemical function remains unknown...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538092/discriminating-residue-substitutions-in-a-single-protein-molecule-using-a-sub-nanopore
#4
Zhuxin Dong, Eamonn Kennedy, Mohammad Hokmabadi, Gregory Timp
It is now possible to create, in a thin inorganic membrane, a single, sub-nanometer-diameter pore, i.e. a sub-nanopore, about the size of an amino acid residue. To explore the prospects for sequencing protein with it, measurements of the force and current were performed as two denatured histones, which differed by four amino acid residue substitutions, were impelled systematically through the sub-nanopore one-at-a-time using an atomic force microscope. The force measurements revealed that once the denatured protein, stabilized by sodium dodecyl sulfate (SDS), translocated through the sub-nanopore, a disproportionately large force was required to pull it back...
May 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28537725/the-color-of-cation-%C3%AF-interactions-subtleties-of-amine-tryptophan-interaction-energetics-allow-for-radical-like-visible-absorbance-and-fluorescence
#5
Laura J Juszczak, Azaria S Eisenberg
Several peptides and a protein with an inter- or intramolecular cation-π interaction between tryptophan (Trp) and an amine cation are shown to absorb and fluoresce in the visible region of the spectrum. Titration of indole with sodium hydroxide or ammonium hydroxide yields an increasing visible fluorescence as well. Visible absorption and multi-peaked fluorescence excitation spectra correlate with experimental absorption spectra and the vibrational modes of calculated absorption spectra for the neutral Trp radical...
May 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28537708/nonsynonymous-polymorphisms-in-the-human-as3mt-arsenic-methylation-gene-implications-for-arsenic-toxicity
#6
Jiaojiao Li, Charles Packianathan, Toby G Rossman, Barry P Rosen
Arsenic methylation, the primary biotransformation in the human body, is catalyzed by the enzyme As(III) S-adenosylmethionine (SAM) methyltransferases (hAS3MT). This process is thought to be protective from acute high-level arsenic exposure. However, with long term low-level exposure, hAS3MT produces intracellular methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)), which are considerably more toxic than inorganic As(III) and may contribute to arsenic-related diseases. Several single nucleotide polymorphisms (SNPs) in putative regulatory elements of the hAS3MT gene have been shown to be protective...
May 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28535668/stability-of-retroviral-vectors-against-ultracentrifugation-is-determined-by-the-viral-internal-core-and-envelope-proteins-used-for-pseudotyping
#7
Soo-Hyun Kim, Kwang-Il Lim
Retroviral and lentiviral vectors are mostly pseudotyped and often purified and concentrated via ultracentrifugation. In this study, we quantified and compared the stabilities of retroviral [murine leukemia virus (MLV)-based] and lentiviral [human immunodeficiency virus (HIV)-1-based] vectors pseudotyped with relatively mechanically stable envelope proteins, vesicular stomatitis virus glycoproteins (VSVGs), and the influenza virus WSN strain envelope proteins against ultracentrifugation. Lentiviral genomic and functional particles were more stable than the corresponding retroviral particles against ultracentrifugation when pseudotyped with VSVGs...
May 2, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28535347/preparation-and-characterization-of-protein-loaded-electrospun-fiber-mat-and-its-release-kinetics
#8
Peng Wen, Yan Wen, Xiao Huang, Minhua Zong, Hong Wu
For the enhancement of protein's bioavailability, a specific delivery system was developed by coaxial electrospinning. Bovine serum albumin (BSA) was used as protein model and the core-sheath fiber mat was fabricated using sodium alginate as shell layer and the BSA-loaded chitosan nanoparticle that prepared previously as core layer. By optimizing electrospinning parameters, uniform fibers with diameters ranging from 200 nm to 600 nm were obtained, and transmission electron microscopy and confocal laser scanning microscopy revealed its core-sheath structure...
May 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28535199/genotype-phenotype-correlation-in-patients-with-isovaleric-acidemia-comparative-structural-modelling-and-computational-analysis-of-novel-variants
#9
Osama K Zaki, George Priya Doss C, Salsabil A Ali, Ghadeer G Murad, Shaima A Elashi, Maryam Sa Ebnou, D Thirumal Kumar, Ola Khalifa, Radwa Gamal, Heba S A El Abd, Bilal N Nasr, Hatem Zayed
Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism. It is caused by a deficiency in the mitochondrial isovaleryl-CoA dehydrogenase (IVD) enzyme. In this study, we investigated eight patients with IVA. The patients diagnoses were confirmed by urinary organic acid analysis and the blood C5-Carnitine value. A molecular genetic analysis of the IVD gene revealed nine different variants: five were missense variants (c.1193G>A; p. R398Q, c.1207T>A; p. Y403N, c.872C>T; p...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28535012/neokestose-suppresses-the-growth-of-human-melanoma-a2058-cells-via-inhibition-of-the-nuclear-factor%C3%A2-%C3%AE%C2%BAb-signaling-pathway
#10
Jiann-Shing Wu, Jan-Yi Chang, C Will Chen, Ming-Tse Lin, Dey-Chyi Sheu, Shun-Mei Lee
Neokestose has superior prebiotic effects compared with the commercial fructooligosaccharides (FOS). In addition, the branched structure of neokestose, a type of neo‑FOS, confers improved chemical stability compared with conventional FOS; therefore, the investigation of the branched structure by the present study may be of high biomedical value. The present study aimed to determine whether neokestose may suppress growth of the A2058 melanoma cell line. The cells were initially treated with neokestose; subsequently, in vitro cytotoxicity was assessed using MTT, and cell cycle progression and apoptosis were detected using flow cytometry...
May 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534617/comparative-proteomics-reveals-timely-transport-into-cilia-of-regulators-or-effectors-as-a-mechanism-underlying-ciliary-disassembly
#11
Limei Wang, Lixiao Gu, Dan Meng, Qiong Wu, Haiteng Deng, Junmin Pan
Primary cilia are assembled and disassembled during cell cycle progression. During ciliary disassembly, ciliary axonemal microtubules (MTs) are depolymerized accompanied with extensive posttranslational protein modifications of ciliary proteins including protein phosphorylation, methylation and ubiquitination. These events are hypothesized to involve transport of effectors or regulators into cilia at the time of ciliary disassembly from the cell body. To prove this hypothesis and identify new proteins involved in ciliary disassembly, we analyzed disassembling flagella in Chlamydomonas using comparative proteomics with TMT labeling...
May 23, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28534590/generation-of-wheat-gluten-hydrolysates-with-dipeptidyl-peptidase-iv-dpp-iv-inhibitory-properties
#12
A B Nongonierma, M Hennemann, S Paolella, R J FitzGerald
Wheat gluten, a Pro-rich dietary protein, was investigated for its potential to produce dipeptidyl peptidase IV (DPP-IV) inhibitory peptides during enzymatic hydrolysis with Debitrase HYW20. Nine gluten hydrolysates (H1-H9) were generated using a 2 factor × 3 level design of experiments (DOE) including the incubation temperature (40, 50 and 60 °C) and the enzyme: substrate ratio (E : S, 0.5, 1.0 and 1.5% (w/w)). Their DPP-IV half maximal inhibitory concentration (IC50) ranged from 0.24 ± 0.02 (H9) to 0...
May 23, 2017: Food & Function
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#13
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534479/efficient-protein-production-inspired-by-how-spiders-make-silk
#14
Nina Kronqvist, Médoune Sarr, Anton Lindqvist, Kerstin Nordling, Martins Otikovs, Luca Venturi, Barbara Pioselli, Pasi Purhonen, Michael Landreh, Henrik Biverstål, Zigmantas Toleikis, Lisa Sjöberg, Carol V Robinson, Nicola Pelizzi, Hans Jörnvall, Hans Hebert, Kristaps Jaudzems, Tore Curstedt, Anna Rising, Jan Johansson
Membrane proteins are targets of most available pharmaceuticals, but they are difficult to produce recombinantly, like many other aggregation-prone proteins. Spiders can produce silk proteins at huge concentrations by sequestering their aggregation-prone regions in micellar structures, where the very soluble N-terminal domain (NT) forms the shell. We hypothesize that fusion to NT could similarly solubilize non-spidroin proteins, and design a charge-reversed mutant (NT*) that is pH insensitive, stabilized and hypersoluble compared to wild-type NT...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534408/modulation-of-the-conformational-dynamics-of-apo-adenylate-kinase-through-a-%C3%AF-cation-interaction
#15
Ritaban Halder, Rabindra Nath Manna, Sandipan Chakraborty, Biman Jana
Large scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in such a way that closely resembles open to closed conformational transition. Here, equilibrium simulations, free energy simulations, QM/MM calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. Apart from its conventional open state, E...
May 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28533982/lid-opening-and-conformational-stability-of-t1-lipase-is-mediated-by-increasing-chain-length-polar-solvents
#16
Jonathan Maiangwa, Mohd Shukuri Mohamad Ali, Abu Bakar Salleh, Raja Noor Zaliha Raja Abd Rahman, Yahaya M Normi, Fairolniza Mohd Shariff, Thean Chor Leow
The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%...
2017: PeerJ
https://www.readbyqxmd.com/read/28533957/pld2-regulates-microtubule-stability-and-spindle-migration-in-mouse-oocytes-during-meiotic-division
#17
Xiaoyu Liu, Xiaoyun Liu, Dandan Chen, Xiuying Jiang, Wei Ma
Phospholipase D2 (PLD2) is involved in cytoskeletal reorganization, cell migration, cell cycle progression, transcriptional control and vesicle trafficking. There is no evidence about PLD2 function in oocytes during meiosis. Herein, we analyzed PLD2 expression and its relationship with spindle formation and positioning in mouse oocyte meiosis. High protein level of PLD2 was revealed in oocytes by Western blot, which remained consistently stable from prophase I with intact germinal vesicle (GV) up to metaphase II (MII) stage...
2017: PeerJ
https://www.readbyqxmd.com/read/28533793/exogenous-supplementation-of-silicon-improved-the-recovery-of-hyperhydric-shoots-in-dianthus-caryophyllus-l-by-stabilizing-the-physiology-and-protein-expression
#18
Prabhakaran Soundararajan, Abinaya Manivannan, Yoon S Cho, Byoung R Jeong
Hyperhydricity is one of the major problems hindering in vitro propagation of Dianthus caryophyllus L. Silicon (Si) is a well-known beneficial element renowned for its stress amelioration properties in plants. This study has demonstrated the physiological and molecular mechanism behind the Si-mediated recovery from hyperhydricity in D. caryophyllus L. 'Green Beauty'. Four weeks old hyperhydric shoots obtained from temporary immersion system were cultured on the Murashige and Skoog medium supplemented with 0 (control), 1...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28533511/cd47-surface-stability-is-sensitive-to-actin-disruption-prior-to-inclusion-within-the-band-3-macrocomplex
#19
Kathryn E Mordue, Bethan R Hawley, Timothy J Satchwell, Ashley M Toye
CD47 is an important 'marker of self' protein with multiple isoforms produced though alternative splicing that exhibit tissue-specific expression. Mature erythrocytes express CD47 isoform 2 only, with membrane stability of this version dependent on inclusion within the band 3 macrocomplex, via protein 4.2. At present a paucity of information exists regarding the associations and trafficking of the CD47 isoforms during erythropoiesis. We show that CD47 isoform 2 is the predominant version maintained at the surface of expanding and terminally differentiating erythroblasts...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533368/bio-inspired-self-healing-structural-color-hydrogel
#20
Fanfan Fu, Zhuoyue Chen, Ze Zhao, Huan Wang, Luoran Shang, Zhongze Gu, Yuanjin Zhao
Biologically inspired self-healing structural color hydrogels were developed by adding a glucose oxidase (GOX)- and catalase (CAT)-filled glutaraldehyde cross-linked BSA hydrogel into methacrylated gelatin (GelMA) inverse opal scaffolds. The composite hydrogel materials with the polymerized GelMA scaffold could maintain the stability of an inverse opal structure and its resultant structural colors, whereas the protein hydrogel filler could impart self-healing capability through the reversible covalent attachment of glutaraldehyde to lysine residues of BSA and enzyme additives...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
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