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https://www.readbyqxmd.com/read/29352227/ly2087101-and-dfbr-share-transmembrane-binding-sites-in-the-%C3%AE-4-3-%C3%AE-2-2-nicotinic-acetylcholine-receptor
#1
Farah Deba, Hamed I Ali, Abisola Tairu, Kara Ramos, Jihad Ali, Ayman K Hamouda
Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have potential therapeutic application in neuropathologies associated with decrease in function or loss of nAChRs. In this study, we characterize the pharmacological interactions of the nAChRs PAM, LY2087101, with the α4β2 nAChR using mutational and computational analyses. LY2087101 potentiated ACh-induced currents of low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs with similar potencies albeit to a different maximum potentiation (potentiation I max  = ~840 and 450%, respectively)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351720/structural-interconversion-in-alzheimer-s-amyloid-%C3%AE-16-35-peptide-in-an-aqueous-solution
#2
Nelson Alves, Rafael B Frigori
Structural properties of Aβ(16-35) fragment are investigated as a model for the amyloid-β peptide excluding its coil-inducing terminals. Our Replica-Exchange Molecular Dynamics simulations using all-atoms and explicit aqueous solvation widely reduce any structural bias. The principal folding pathway shows direct conversion of coil to β-sheet, without the long proposed helix intermediates. Our PCA analysis indicates that the fragment is also intrinsically disordered, as the full amyloid-β peptide. Thus, the observed folding mechanism lacks free-energy barriers and any peaks in the thermal capacity...
January 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29350420/over-expression-of-dec1-inhibits-myogenic-differentiation-by-modulating-myog-activity-in-bovine-satellite-cell
#3
Yongzhen Huang, Xinsheng Lai, Linyong Hu, Chuzhao Lei, Xianyong Lan, Chunlei Zhang, Yun Ma, Li Zheng, Yue-Yu Bai, Fengpeng Lin, Hong Chen
Differentiated embryo chondrocyte 1 (DEC1), a member of basic-helix-loop-helix transcription factor Bhlhe40, also called stimulated by retinoic acid 13, STRA13, plays an important role in the regulation of adipogenesis, tumorigenesis, peripheral circadian output, response to hypoxia and development of metabolic syndrome. Previous studies suggested that DEC1 was involved in skeletal muscle development; however, its precise role in myoblast differentiation has not been determined. In the present study, we showed that DEC1 expressed ubiquitously in different bovine tissues and was down-regulated in differentiated bovine satellite cells...
January 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29350285/gut-shuttle-service-endozoochory-of-dispersal-limited-soil-fauna-by-gastropods
#4
Manfred Türke, Markus Lange, Nico Eisenhauer
Numerous important ecosystem functions and services depend on soil biodiversity. However, little is known about the mechanisms which maintain the vast belowground biodiversity and about the filters shaping soil community composition. Yet, biotic interactions like facilitation and dispersal by animals are assumed to play a crucial role, particularly as most soil animal taxa are strongly limited in their active dispersal abilities. Here, we report on a newfound interaction of potentially high ubiquity and importance in soil communities: the endozoochorous dispersal of soil fauna by gastropods...
January 19, 2018: Oecologia
https://www.readbyqxmd.com/read/29350033/impact-of-backbone-pattern-and-residue-substitution-on-helicity-in-%C3%AE-%C3%AE-%C3%AE-peptides
#5
Young-Hee Shin, Samuel H Gellman
We have evaluated the impact of changes in the chemical structure of peptidic oligomers containing α-, β-, and γ-amino acid residues (α/β/γ-peptides) on the propensities of these oligomers to adopt helical conformations in aqueous and alcoholic solutions. These studies were inspired by our previous discovery that α/β/γ-peptides containing a regular αγααβα hexad repeat adopt an α-helix-like conformation in which the β and γ residues are aligned in a stripe along one side, and the remainder of the helix surface is defined by the α residues...
January 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29348202/molecular-characterization-of-latent-gdf8-reveals-mechanisms-of-activation
#6
Ryan G Walker, Jason C McCoy, Magdalena Czepnik, Melanie J Mills, Adam Hagg, Kelly L Walton, Thomas R Cotton, Marko Hyvönen, Richard T Lee, Paul Gregorevic, Craig A Harrison, Thomas B Thompson
Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is "spring-loaded...
January 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29347050/manipulation-of-double-stranded-dna-melting-by-force
#7
Amit Raj Singh, Rony Granek
By integrating elasticity-as described by the Gaussian network model-with bond binding energies that distinguish between different base-pair identities and stacking configurations, we study the force induced melting of a double-stranded DNA (dsDNA). Our approach is a generalization of our previous study of thermal dsDNA denaturation [J. Chem. Phys. 145, 144101 (2016)JCPSA60021-960610.1063/1.4964285] to that induced by force at finite temperatures. It allows us to obtain semimicroscopic information about the opening of the chain, such as whether the dsDNA opens from one of the ends or from the interior, forming an internal bubble...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346958/electroclinic-effect-in-chiral-smectic-a-liquid-crystal-elastomers
#8
Noy Cohen, Kaushik Bhattacharya
Chiral smectic-A liquid crystal elastomers are rubbery materials composed of a lamellar arrangement of liquid crystalline mesogens. It has been shown experimentally that these materials shear when subjected to an electric field due to the electrically induced tilt of the director. Experiments have also shown that shearing a chiral smectic-A elastomer gives rise to a polarization. Roughly, the shear force tilts the directors which, in turn, induce electric dipoles. This paper builds on previous works and models the electromechanical response of smectic-A elastomers using free energy contributions that are associated with the lamellar structure, the relative tilt between the director and the layer normal, and the coupling between the director and the electric field...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346883/force-spectroscopy-unravels-the-role-of-ionic-strength-on-dna-cisplatin-interaction-modulating-the-binding-parameters
#9
L Oliveira, M S Rocha
In the present work we have gone a step forward in the understanding of the DNA-cisplatin interaction, investigating the role of the ionic strength on the complexes formation. To achieve this task, we use optical tweezers to perform force spectroscopy on the DNA-cisplatin complexes, determining their mechanical parameters as a function of the drug concentration in the sample for three different buffers. From such measurements, we determine the binding parameters and study their behavior as a function of the ionic strength...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346615/the-rna-splicing-endonuclease-from-the-euryarchaeaon-methanopyrus-kandleri-is-a-heterotetramer-with-constrained-substrate-specificity
#10
Ayano Kaneta, Kosuke Fujishima, Wataru Morikazu, Hiroyuki Hori, Akira Hirata
Four different types (α4, α'2, (αβ)2 and ε2) of RNA-splicing endonucleases (EndAs) for RNA processing are known to exist in the Archaea. Only the (αβ)2 and ε2 types can cleave non-canonical introns in precursor (pre)-tRNA. Both enzyme types possess an insert associated with a specific loop, allowing broad substrate specificity in the catalytic α units. Here, the hyperthermophilic euryarchaeon Methanopyrus kandleri (MKA) was predicted to harbor an (αβ)2-type EndA lacking the specific loop. To characterize MKA EndA enzymatic activity, we constructed a fusion protein derived from MKA α and β subunits (fMKA EndA)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346445/transcriptome-analysis-of-skin-fibroblasts-with-dominant-negative-col3a1-mutations-provides-molecular-insights-into-the-etiopathology-of-vascular-ehlers-danlos-syndrome
#11
Nicola Chiarelli, Giulia Carini, Nicoletta Zoppi, Marco Ritelli, Marina Colombi
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures...
2018: PloS One
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#12
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345707/synthesis-and-characterization-of-a-photocleavable-collagen-like-peptide
#13
Alfredo Ornelas, Kaitlyn N Williams, Kevin A Hatch, Aurelio Paez, Angela C Aguilar, Cameron C Ellis, Nishat Tasnim, Supriyo Ray, Carl W Dirk, Thomas Boland, Binata Joddar, Chunqiang Li, Katja Michael
A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution. Illumination of a thin film of the peptide, or a thin film of a photoreactive amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with femtosecond laser light at 710 nm allows for the creation of well-resolved micropatterns...
January 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29344948/glycation-of-ovalbumin-after-high-intensity-ultrasound-pretreatment-effects-on-conformation-igg-ige-binding-ability-and-antioxidant-activity
#14
Wenhua Yang, Zongcai Tu, Hui Wang, Lu Zhang, Qidong Song
BACKGROUND: Ovalbumin (OVA), a protein with excellent nutritional and processing properties, is the major allergen of hen egg white. Previous study showed that high-intensity ultrasound treatment increased the IgG and IgE binding abilities by unfolding the conformational structure of OVA. It may allow modifying the IgG and IgE binding of OVA by combining high-intensity ultrasound with other methods, such as glycation, a promising method for the improvement of protein properties. RESULTS: Glycation with mannose (M) after ultrasound pretreatment at 0-600 W significantly reduced the IgG and IgE binding abilities and dramatically enhanced the antioxidant activity of OVA-M conjugates, with the lowest values of IgG and IgE binding and highest values of antioxidant capacity observed at 600W...
January 18, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29344585/hereditary-folate-malabsorption-due-to-a-mutation-in-the-external-gate-of-the-proton-coupled-folate-transporter-slc46a1
#15
Srinivas Aluri, Rongbao Zhao, Charlotte Lubout, Susanna M I Goorden, Andras Fiser, I David Goldman
Hereditary folate malabsorption (HFM) is an autosomal recessive disorder characterized by impaired intestinal folate absorption and impaired folate transport across the choroid plexus due to loss of function of the proton-coupled folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM, affecting a residue located in the 11th transmembrane helix within the external gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had sufficient residual activity to characterize the transport defect and the structural requirements at this site for gate function...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29344195/collagen-triple-helix-repeat-containing-1-promotes-tumor-angiogenesis-in-gastrointestinal-stromal-tumors
#16
Seng Wang Fu, Hai Ying Chen, Xiao Lu Lin, Li Yang, Zhi Zheng Ge
Collagen triple helix repeat containing 1 (Cthrc1) is a secreted protein that has been observed to lead to poorer prognosis by inducing the invasion and metastasis in different tumors; however, it has not been demonstrated that Cthrc1 is involved in tumor angiogenesis. Immunohistochemical staining of Cthrc1 and CD31 in gastrointestinal stromal tumor tissue demonstrated that Cthrc1 is associated with microvascular density. Overexpression of Cthrc1 protein may alter the properties of human umbilical vein endothelial cells (HUVECs), including migration, invasion, tubule formation and aortic ring sprouting...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343645/crystal-structure-of-the-mammalian-lipopolysaccharide-detoxifier
#17
Alexei Gorelik, Katalin Illes, Bhushan Nagar
LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343545/tolloid-cleavage-activates-latent-gdf8-by-priming-the-pro-complex-for-dissociation
#18
Viet Q Le, Roxana E Iacob, Yuan Tian, William McConaughy, Justin Jackson, Yang Su, Bo Zhao, John R Engen, Michelle Pirruccello-Straub, Timothy A Springer
Growth differentiation factor 8 (GDF8)/myostatin is a latent TGF-β family member that potently inhibits skeletal muscle growth. Here, we compared the conformation and dynamics of precursor, latent, and Tolloid-cleaved GDF8 pro-complexes to understand structural mechanisms underlying latency and activation of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro-complexes reveals a V-shaped conformation that is unaltered by furin cleavage and sharply contrasts with the ring-like, cross-armed conformation of latent TGF-β1...
January 17, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29343087/sulfhydrated-sirtuin-1-increasing-its-deacetylation-activity-is-an-essential-epigenetics-mechanism-of-anti-atherogenesis-by-hydrogen-sulfide
#19
Congkuo Du, Xianjuan Lin, Wenjing Xu, Fengjiao Zheng, Junyan Cai, Jichun Yang, Qinghua Cui, Chaoshu Tang, Jun Cai, Guoheng Xu, Bin Geng
AIMS: Hydrogen sulfide (H2S) has a protective role in the pathogenesis of atherosclerosis by multiple pathways. Sirtuin-1 (SIRT1) is a histone deacetylase, as an essential mediated longevity gene, and has an anti-atherogenic effect by regulating the acetylation of some functional proteins. Whether SIRT1 is involved in protecting H2S in atherosclerosis and its mechanism remains unclear. RESULTS: In ApoE-knockout atherosclerosis mice, treatment with an H2S donor (NaHS or GYY4137) reduced atherosclerotic plaque area, macrophage infiltration, aortic inflammation and plasma lipid level...
January 17, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29342326/mixed-fluorotryptophan-substitutions-at-the-same-residue-expand-the-versatility-of-%C3%A2-%C3%A2-f-protein-nmr-spectroscopy
#20
Calem Kenward, Kyungsoo Shin, Jan Rainey
The strategy of applying fluorine NMR to characterize ligand binding to a membrane protein prepared with mixtures of tryptophans substituted with F at different positions on the indole ring was tested. The ¹⁹F NMR behavior of 4-, 5-, 6-, and 7-fluorotryptophan were directly compared as a function of both micellar environment and fragment size for two overlapping apelin receptor (AR/APJ) segments - one with a single transmembrane (TM) helix and two tryptophan residues, the other with three TM helices and two additional tryptophan residues...
January 17, 2018: Chemistry: a European Journal
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