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https://www.readbyqxmd.com/read/28209477/characterizing-the-biological-and-biochemical-profile-of-six-different-scorpion-venoms-from-the-buthidae-and-scorpionidae-family
#1
Sebastian Estrada-Gómez, Lyz Gomez-Rave, Leidy Vargas-Muñoz, Arie van der Meijden
The objective of this study was to characterize a selection of six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28208612/enteric-pathogens-and-their-toxin-induced-disruption-of-the-intestinal-barrier-through-alteration-of-tight-junctions-in-chickens
#2
REVIEW
Wageha A Awad, Claudia Hess, Michael Hess
Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird's health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells...
February 10, 2017: Toxins
https://www.readbyqxmd.com/read/28202723/mapping-of-voltage-sensor-positions-in-resting-and-inactivated-mammalian-sodium-channels-by-lret
#3
Tomoya Kubota, Thomas Durek, Bobo Dang, Rocio K Finol-Urdaneta, David J Craik, Stephen B H Kent, Robert J French, Francisco Bezanilla, Ana M Correa
Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct)...
February 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202361/pre-clinical-evaluation-of-voltage-gated-calcium-channel-blockers-derived-from-the-spider-p-%C3%A2-nigriventer-in-glioma-progression
#4
Natália Fontana Nicoletti, Thaís Cristina Erig, Rafael Fernandes Zanin, Marcelo Ricardo Roxo, Nelson Pires Ferreira, Marcus Vinicius Gomez, Fernanda Bueno Morrone, Maria Martha Campos
This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1β from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28196960/repair-of-a-bacterial-small-%C3%AE-barrel-toxin-pore-depends-on-channel-width
#5
Gisela von Hoven, Amable J Rivas, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sapun Parekh, Nadja Hellmann, Matthias Husmann
Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca(2+) influx, lysosomal exocytosis, and membrane repair...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28195225/a-novel-bk-channel-targeted-peptide-suppresses-sound-evoked-activity-in-the-mouse-inferior-colliculus
#6
L L Scott, E J Brecht, A Philpo, S Iyer, N S Wu, S J Mihic, R W Aldrich, J Pierce, J P Walton
Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194851/inversion-of-the-side-chain-stereochemistry-of-indvidual-thr-or-ile-residues-in-a-protein-molecule-impact-on-the-folding-stability-and-structure-of-the-shk-toxin
#7
Bobo Dang, Rong Shen, Tomoya Kubota, Kalyaneswar Mandal, Francisco Bezanilla, Benoit Roux, Stephen B H Kent
ShK toxin is a cysteine-rich 35-residue protein ion-channel ligand isolated from the sea anemone Stichodactyla helianthus. In this work, we studied the effect of inverting the side chain stereochemistry of individual Thr or Ile residues on the properties of the ShK protein. Molecular dynamics simulations were used to calculate the free energy cost of inverting the side-chain stereochemistry of individual Thr or Ile residues. Guided by the computational results, we used chemical protein synthesis to prepare three ShK polypeptide chain analogues, each containing either an allo-Thr or an allo-Ile residue...
February 14, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28192089/dynamic-phenylalanine-clamp-interactions-define-single-channel-polypeptide-translocation-through-the-anthrax-toxin-protective-antigen-channel
#8
Koyel Ghosal, Jennifer M Colby, Debasis Das, Stephen T Joy, Paramjit S Arora, Bryan A Krantz
Anthrax toxin is an intracellularly acting toxin where sufficient detail is known about the structure of its channel, allowing for molecular investigations of translocation. The toxin is comprised of three proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF). The toxin's translocon, PA, translocates the large enzymes, LF and EF, across the endosomal membrane into the host cell's cytosol. Polypeptide clamps located throughout the PA channel catalyze the translocation of LF and EF. Here we show that the central peptide clamp, the ϕ clamp, is a dynamic site that governs the overall peptide translocation pathway...
February 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28183995/structure-of-a-eukaryotic-voltage-gated-sodium-channel-at-near-atomic-resolution
#9
Huaizong Shen, Qiang Zhou, Xiaojing Pan, Zhangqiang Li, Jianping Wu, Nieng Yan
Voltage-gated sodium (Nav) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryo-EM structure of a putative Nav channel from American cockroach (designated NavPaS) at 3.8-Å resolution. The voltage sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops...
February 9, 2017: Science
https://www.readbyqxmd.com/read/28181561/peripheral-sensory-neuron-injury-contributes-to-neuropathic-pain-in-experimental-autoimmune-encephalomyelitis
#10
I-Ching Wang, Chen-Yen Chung, Fang Liao, Chih-Cheng Chen, Cheng-Han Lee
Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179976/biobetters-from-an-integrated-computational-experimental-approach
#11
REVIEW
Serdar Kuyucak, Veysel Kayser
Biobetters are new drugs designed from existing peptide or protein-based therapeutics by improving their properties such as affinity and selectivity for the target epitope, and stability against degradation. Computational methods can play a key role in such design problems-by predicting the changes that are most likely to succeed, they can drastically reduce the number of experiments to be performed. Here we discuss the computational and experimental methods commonly used in drug design problems, focusing on the inverse relationship between the two, namely, the more accurate the computational predictions means the less experimental effort is needed for testing...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28159581/recombinant-expression-of-intrepicalcin-from-the-scorpion-vaejovis-intrepidus-and-its-effect-on-skeletal-ryanodine-receptors
#12
Leonel Vargas-Jaimes, Liang Xiao, Jing Zhang, Lourival D Possani, Héctor H Valdivia, Verónica Quintero-Hernández
BACKGROUND: Scorpion venoms contain toxins that modulate ionic channels, among which are the calcins, a small group of short, basic peptides with an Inhibitor Cystine Knot (ICK) motif that target calcium release channels/ryanodine receptors (RyRs) with high affinity and selectivity. Here we describe the heterologous expression of Intrepicalcin, identified by transcriptomic analysis of venomous glands from Vaejovis intrepidus. METHODS: Recombinant Intrepicalcin was obtained in Escherichia coli BL21-DE3 (periplasm) by fusing the Intrepicalcin gene to sequences coding for signal-peptide, thioredoxin, His-tag and enterokinase cleavage site...
January 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28155242/sensory-neuron-regulation-of-gastrointestinal-inflammation-and-bacterial-host-defence
#13
N Y Lai, K Mills, I M Chiu
Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage...
February 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28143758/hanatoxin-inserts-into-phospholipid-membranes-without-pore-formation
#14
Kuo-Long Lou, Meng-Hsuan Hsieh, Wei-Jung Chen, Yu-Che Cheng, Jia-Nan Jian, Ming-Tao Lee, Tsang-Lang Lin, Yu-Shuan Shiau, Horng-Huei Liou
Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding...
January 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28139934/oriented-reconstitution-of-the-full-length-kcsa-potassium-channel-in-a-lipid-bilayer-for-afm-imaging
#15
Ayumi Sumino, Takayuki Uchihashi, Shigetoshi Oiki
Here, we have developed a method of oriented reconstitution of the KcsA potassium channel amenable to high-resolution AFM imaging. The solubilized full-length KcsA channels with histidine-tagged (His-tag) C-terminal ends were attached to a Ni(2+)-coated mica surface, and then detergent-destabilized liposomes were added to fill the interchannel space. AFM revealed that the membrane-embedded KcsA channels were oriented with their extracellular faces upward, seen as a tetrameric square shape. This orientation was corroborated by the visible binding of a peptide scorpion toxin, agitoxin-2...
February 1, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28132918/ciproxifan-a-histamine-h3-receptor-antagonist-and-inverse-agonist-presynaptically-inhibits-glutamate-release-in-rat-hippocampus
#16
Cheng-Wei Lu, Tzu-Yu Lin, Chia-Ying Chang, Shu-Kuei Huang, Su-Jane Wang
Ciproxifan is an H3 receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Cav2...
January 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28131838/phospholipase-c-dependent-hydrolysis-of-phosphatidylinositol-4-5-bisphosphate-underlies-agmatine-induced-suppression-of-n-type-ca-2-channel-in-rat-celiac-ganglion-neurons
#17
Young-Hwan Kim, Ji-Hyun Jeong, Duck-Sun Ahn, Seungsoo Chung
Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (ICav2.2) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited ICav2.2 in a VI manner. The agmatine-induced inhibition of the ICav2...
January 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28130397/melt-with-this-kiss-paralysing-and-liquefying-venom-of-the-assassin-bug-pristhesancus-plagipennis-hemiptera-reduviidae
#18
Andrew A Walker, Bruno Madio, Jiayi Jin, Eivind A B Undheim, Bryan G Fry, Glenn F King
Assassin bugs (Hemiptera: Heteroptera: Reduviidae) are venomous insects, most of which prey on invertebrates. Assassin bug venom has features in common with venoms from other animals, such as paralysing and lethal activity when injected, and a molecular composition that includes disulfide-rich peptide neurotoxins. Uniquely, this venom also has strong liquefying activity that has been hypothesised to facilitate feeding through the narrow channel of the proboscis - a structure inherited from sap- and phloem-feeding phytophagous hemipterans and adapted during the evolution of Heteroptera into a fang and feeding structure...
January 27, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28124609/recombinant-expression-functional-characterization-of-two-scorpion-venom-toxins-with-three-disulfide-bridges-from-the-chinese-scorpion-buthus-martensii-karsch
#19
ShengGuo Lin, XueLin Wang, XueYao Hu, YongShan Zhao, MingYi Zhao, JingHai Zhang, Yong Cui
Scorpion venom contains a large variety of biologically active peptides. However, most of these peptides have not been identified and characterized. Peptides with three disulfide bridges, existing in the scorpion venom, have not been studied in detail and have been poorly characterized until now. Here, we report the recombinant expression and functional characterization of two kinds of venom peptides (BmKBTx and BmNaL-3SS2) with three disulfide bridges. This study adopted an effective E. coli system. The genes for BmKBTx and BmNaL-3SS2 were obtained by the Polymerase Chain Reaction method and finally cloned to the pSYPU-1b vector...
January 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28122730/distinct-physiological-effects-of-%C3%AE-1-and-%C3%AE-2-adrenoceptors-in-mouse-ventricular-myocytes-insights-from-a-compartmentalized-mathematical-model
#20
Kelvin Rozier, Vladimir E Bondarenko
The β1- and β2-adrenergic signaling systems play different roles in the functioning of cardiac cells. Experimental data shows that the activation of β1-adrenergic signaling system produces significant inotropic, lusitropic, and chronotropic effects in the heart, while the effects of the β2-adrenergic signaling system is less apparent. In this paper, a comprehensive compartmentalized experimentally-based mathematical model of the combined β1- and β2-adrenergic signaling systems in mouse ventricular myocytes is developed to simulate the experimental findings and make testable predictions of the behavior of the cardiac cells under different physiological conditions...
January 25, 2017: American Journal of Physiology. Cell Physiology
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