Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCORPIONS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed2004

Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins.

Maurotoxin (MTX) and HsTx1 are two scorpion toxins belonging to the alpha-KTx6 structural family. These 34-residue toxins, cross-linked by four disulfide bridges, share 59% sequence identity and fold along the classical alpha/beta scaffold. Despite these structural similarities, they fully differ in their pharmacological profiles. MTX is highly active on small (SK) and intermediate (IK) conductance Ca(2+)-activated (K(+)) channels and on voltage-gated Kv1.2 channel, whereas HsTx1 potently blocks voltage-gated Kv1.1 and Kv1.3 channels only. Here, we designed and chemically produced MTX-HsTx1, a chimera of both toxins that contains the N-terminal helical region of MTX (sequence 1-16) and the C-terminal beta-sheet region of HsTx1 (sequence 17-34). The three-dimensional structure of the peptide in solution was solved by (1)H NMR. MTX-HsTx1 displays the activity of MTX on SK channel, whereas it exhibits the pharmacological profile of HsTx1 on Kv1.1, Kv1.2, Kv1.3, and IK channels. These data demonstrate that the helical region of MTX exerts a key role in SK channel recognition, whereas the beta-sheet region of HsTx1 is crucial for activity on all other channel types tested.

Amino Acid Sequence↗
PubMed2005

A variable residue in the pore of Kv1 channels is critical for the high affinity of blockers from sea anemones and scorpions.

Animal toxins are associated with well defined selectivity profiles; however the molecular basis for this property is not understood. To address this issue we refined our previous three-dimensional models of the complex between the sea anemone toxin BgK and the S5-S6 region of Kv1.1 (Gilquin, B., Racape, J., Wrisch, A., Visan, V., Lecoq, A., Grissmer, S., Ménez, A., and Gasparini, S. (2002) J. Biol. Chem. 277, 37406-37413) using a docking procedure that scores and ranks the structures by comparing experimental and back-calculated values of coupling free energies DeltaDeltaGint obtained from double-mutant cycles. These models further highlight the interaction between residue 379 of Kv1.1 and the conserved dyad tyrosine residue of BgK. Because the nature of the residue at position 379 varies from one channel subtype to another, we explored how these natural mutations influence the sensitivity of Kv1 channel subtypes to BgK using binding and electrophysiology experiments. We demonstrated that mutations at this single position indeed suffice to abolish or enhance the sensitivity of Kv1 channels for BgK and other sea anemone and scorpion toxins. Altogether, our data suggest that the residue at position 379 of Kv1 channels controls the affinity of a number of blocking toxins.

Amino Acid Substitution↗
PubMed1999

Androctonin, a novel antimicrobial peptide from scorpion Androctonus australis: solution structure and molecular dynamics simulations in the presence of a lipid monolayer.

Androctonin is a highly cationic antimicrobial peptide from scorpion exhibiting a broad spectrum of activities against bacteria and fungi. It contains 25 amino acids including four cysteine residues forming two disulfide bridges. We report here on the determination of its solution structure by conventional two-dimensional (2D) 1H-NMR spectroscopy and molecular modelling using distance geometry and molecular dynamics methods. The structure of androctonin involves a well-defined highly twisted anti-parallel beta-sheet with strands connected by a more variable positively charged turn. A comparison with the structure of tachyplesin I (horseshoe crab) reveals that the amphiphilic character of the protein surface of this homologous peptide is not observed in androctonin. We have undertaken a 200-ps molecular dynamics simulation study on a system including one androctonin molecule and a monolayer of DMPG (1,2-dimyristoylphosphatidylglycerol) lipids. On the basis of this simulation, the first steps of the membrane permeabilization process are discussed.

Amino Acid Sequence↗
PubMed1996

Isolation of toxin TsTX-VI from Tityus serrulatus scorpion venom. Effects on the release of neurotransmitters from synaptosomes.

A detailed procedure for the purification of Tityustoxin-VI, TsTX-VI, from Tityus serrulatus scorpion venom is described. For comparative purposes, a second toxin, CM-VI, obtained from the same fractionation procedure, was analyzed in parallel. Typical biochemical parameters, such as electrophoretic migration, mol.weight, amino acid composition and N-terminal sequence (first 42 amino acid residues out of a total of approx. 60) were determined for both. Our data showed that CM-VI is identical or extremely homologous to gamma-toxin (TsTX-I), the highly toxic major toxin from T. serrulatus venom. TsTX-VI was less toxic, although still effective at inducing an allergic reaction, lacrymation and contraction of the hind legs of mice. Both toxins produced a dose dependent release of the neurotransmitters glutamic acid and gamma aminobutyric acid from rat brain synaptosomes, this effect being blocked by tetrodotoxin.

Animals↗
PubMed1997

TsTX-VII, a new toxin from Tityus serrulatus scorpion venom able to induce the release of neurotransmitters from rat brain synaptosomes not blocked by tetrodotoxin.

A procedure for the isolation of the toxin Tityustoxin VII (TsTX-VII) from Tityus serrulatus scorpion venom and its biochemical characterization is reported. This protein has a M(r) = 6,700-6,800, eight half-cystine residues accounting for four disulfide bridges and no His. Its N-terminal sequence GHZGYGS ... characterizes it as a new toxin, able to release glutamic acid and gamma aminobutyric acid from rat brain synaptosomes "in vitro". This release was also induced by the whole venom. Tetrodotoxin however blocked the effect of the whole venom but not that of TsTX-VII, thus suggesting that the releasing mechanism by TsTX-VII does not involve Na+ but perhaps K+ or Ca++ channels.

Animals↗
PubMed1985

Three-dimensional reconstruction of thick filaments from Limulus and scorpion muscle.

We have produced three dimensional reconstructions, at a nominal resolution of 5 nm, of thick filaments from scorpion and Limulus skeletal muscle, both of which have a right-handed four-stranded helical arrangement of projecting subunits. In both reconstructions there was a distinct division of density within projecting subunits consistent with the presence of two myosin heads. Individual myosin heads appeared to be curved, with approximate dimensions of 16 X 5 X 5 nm and seemed more massive at one end. Our reconstructions were consistent with the two heads in a projecting subunit being arranged either antiparallel or parallel to each other and directed away from the bare zone. Although we cannot exclude the second of these interpretations, we favor the first as being more consistent with both filament models and also because it would enable easy phosphorylation of light chains. The antiparallel interpretation requires that the two heads within a subunit derive from different myosin molecules. In either interpretation, the two heads have different orientations relative to the thick filament shaft.

Animals↗
PubMed1972

Electromechanical coupling in tubular muscle fibers. I. The organization of tubular muscle fibers in the scorpion Leiurus quinquestriatus.

The tubular fibers of the claw-closer muscle of the scorpion have a central core containing nuclei and mitochondria. The myofibrils have the shape of thin lamellae (1 micro) extending radially from the core to the surface membrane (20 micro). The thick myofilaments are organized in a hexagonal array with orbits of 10-13 thin myofilaments. The ratio of thick-to-thin filaments is 1:5. Transverse tubular system (TS) openings are located between lamellated myofibrils. In each sarcomere two TS's are found, one on each side of the H band. The TS is composed of a transverse tubule and tubular pockets (TP). The TP's form diadic contact with the terminal cisternae of the sarcoplasmic reticulum. The TS can be traced from the cell membrane down to the cell core. The surface area of the TS was calculated to be six times that of the outer surface membrane.

Action Potentials↗
PubMed1988

Pandinus imperator scorpion venom blocks voltage-gated potassium channels in GH3 cells.

We examined the effects of Pandinus imperator scorpion venom on voltage-gated potassium channels in cultured clonal rat anterior pituitary cells (GH3 cells) using the gigohm-seal voltage-clamp method in the whole-cell configuration. We found that Pandinus venom blocks the voltage-gated potassium channels of GH3 cells in a voltage-dependent and dose-dependent manner. Crude venom in concentrations of 50-500 micrograms/ml produced 50-70% block of potassium currents measured at -20 mV, compared with 25-60% block measured at +50 mV. The venom both decreased the peak potassium current and shifted the voltage dependence of potassium current activation to more positive potentials. Pandinus venom affected potassium channel kinetics by slowing channel opening, speeding deactivation slightly, and increasing inactivation rates. Potassium currents in cells exposed to Pandinus venom did not recover control amplitudes or kinetics even after 20-40 min of washing with venom-free solution. The concentration dependence of crude venom block indicates that the toxins it contains are effective in the nanomolar range of concentrations. The effects of Pandinus venom were mimicked by zinc at concentrations less than or equal to 0.2 mM. Block of potassium current by zinc was voltage dependent and resembled Pandinus venom block, except that block by zinc was rapidly reversible. Since zinc is found in crude Pandinus venom, it could be important in the interaction of the venom with the potassium channel. We conclude that Pandinus venom contains toxins that bind tightly to voltage-dependent potassium channels in GH3 cells. Because of its high affinity for voltage-gated potassium channels and its irreversibility, Pandinus venom may be useful in the isolation, mapping, and characterization of voltage-gated potassium channels.

Animals↗
PubMed1975

Heterogeneity of the minimum functional unit of hemocyanins from the spider (Argiope bruennichii), the scorpion (Heterometrus sp.), and the horseshoe crab (Tachypleus tridentatus).

The heterogeneity of arthropod hemocyanins was studied by polyacrylamide gel electrophoresis and immunochemical techniques. The spider (Argiope bruennichii), the scorpion (Heterometrus sp.), and the horseshoe crab (Tachypleus tridentatus) were found to have 4, 5, and 5 minimum functional units of hemocyanin, respectively, the apparent molecular weights of which were 79,000, 81000, and 80,000, respectively, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Animals↗
PubMed2003

Sequence and structure-activity relationship of a scorpion venom toxin with nitrergic activity in rabbit corpus cavernosum.

An alpha-toxin responsible for nitric oxide (NO) release in rabbit corpus cavernosum (RbCC) was isolated from Tityus serrulatus venom (TSV). The isolated peptide (molecular mass of 7427.66+/-0.15 Da) was identified as Ts3 after determination of Cys residues, N-terminal amino acid analysis, and proteolytic peptide mapping. Ts3 (30 nM) markedly relaxed the RbCC; this response was blocked by the NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM) and the Na+ channel blocker tetrodotoxin (100 nM). Synthetic peptides based on either Ts3 (P1-16, P17-32, P33-48, P49-64, P9-24, P25-40, P41-56, YGLPDKVPTKT) or Bukatoxin (isolated from Buthus martensi Karsch scorpion venom) sequence (Buka11, Buka11-B, PDKVP, PDSEP) were assayed. These peptides slightly relaxed the RbCC, and such an effect was independent of Na+ channel activation or NO release. Our results indicate that Ts3 exerts nitrergic actions and contributes to the relaxing activity of TSV in RbCC, thus providing a valuable tool to investigate the mechanisms underlying nerve activation in erectile tissues, because NO released from nitrergic fibers plays a key role in the erectile process. Our findings revealed the key importance of the Ts3 structure three-dimensional conformation maintenance for biological activity, because linear peptide sequences neither presented substantial relaxations nor was this effect related to nitrergic activity.

Amino Acid Sequence↗
PubMed1999

Biosensor binding assay of BmK AS-1, a novel Na+ channel-blocking scorpion ligand on rat brain synaptosomes.

The pharmacological binding of BmK AS-1, a novel Na+ channel-specific ligand purified from Chinese scorpion Buthus martensi Karsch (BmK), has been investigated by biosensor assay. The results showed a fast association rate constant (1.14 x 10(4) M(-1) s(-1)) but a very slow dissociation rate constant (3.24 x 10(-5) s(-1)) for BmK AS-1 binding to the Na+ channel on rat brain synaptosomes. The binding of BmK AS-1 to rat brain synaptosomes could be partially competed by BmK IT2, a depressant insect-selective toxin, but not by BmK I, an alpha-like toxin from the same venom. It was thus further demonstrated that BmK AS-1 might bind to a distinct receptor site, which was partially overlapping that for BmK IT2, but different from that of BmK I on rat brain Na+ channels.

Animals↗
PubMed2004

Modulation of intracellular Na+ concentration by BmK AS, a scorpion toxin, in B104 cell line.

ABSL Effects of BmK AS, a toxin from scorpion Buthus mortensi Karsch and an activator of skeletal muscle RyRs, on the intracellular Na+ concentration have been investigated in the B104 neuroblastoma cell line by fluorescence digital imaging techniques. The intracellular Na+ concentration was elevated by 500 nM BmK AS significantly over a 30 min period, and the effect could be enhanced by addition of ouabain. In addition, BmK AS induced a biphasic modulation of [Na+]i in the dose-dependent range from 20 to 500 nM in the presence of ouabain. The results suggest that BmK AS may modulate intracellular signals by altering the intracellular Na+ concentration in the B104 cells.

Animals↗
PubMed2002

Cardiovascular and respiratory interactions of hyperosmolar saline, scorpion toxin, and veratridine in rats.

This study evaluates the cardiovascular and respiratory effects evoked by hypertonic sodium chloride solution (HSS) and the possible interactions of these effects with scorpion toxin (TX) or veratridine (V). Groups 1 (1 mL/kg, rapid), 2 (4 mL/kg, rapid), and 3 (4 mL/kg, slow) were used for comparison of HSS administered by rapid or slow injection. HSS (4 mL/kg) was injected after bilateral vagotomy (group 4) or administration of atropine (group 5). In groups 6 (1 mL/kg in bolus), 7 (4 mL/kg in bolus), and 8 (4 mL/kg/60 s), HSS was injected 20 min after the administration of TX (250 microg/kg). In group 9, two doses of V (25 microg/kg, i.v.) were injected 10 min apart. Concomitantly with the second dose of V, HSS (4 mL/kg) was injected into the jugular vein. HSS administered by rapid injection (1 mL/kg) resulted in hypotension, hyperventilation, and a slight decrease in heart rate. However, when HSS was administered after TX, only bradypnea was observed. HSS (4 mL/kg, rapid) induced a rapid and marked fall in blood pressure, bradycardia, and apnea. However, when HSS was administered after TX, a more pronounced bradycardia and a smaller reduction in mean arterial pressure were observed. Slow injection of HSS (60 s) evoked hypotension, hyperventilation, and bradycardia. The same dose injected after TX resulted in bradypnea and a smaller reduction in blood pressure. The HSS-induced hypotension was attenuated by previous administration of atropine or by vagotomy, whereas bradycardia was prevented by previous injection of atropine, but not by bilateral vagotomy. Like vagotomy, atropinization prevented the apnea and bradypnea produced by HSS (4 mL/kg in bolus). V evoked a slight bradycardia, hypotension, and apnea. These effects were potentiated when V was injected concomitantly with HSS. The effects of HSS are dependent on both volume and speed of injection, and are affected by previous injection of TX or concomitant injection of V.

Animals↗
PubMed2000

Towards the charge-density study of proteins: a room-temperature scorpion-toxin structure at 0.96 A resolution as a first test case.

The number of protein structures refined at a resolution higher than 1.0 A is continuously increasing. Subatomic structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 A) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The structure of the scorpion Androctonus australis Hector toxin II has been refined at 0.96 A resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.

Crystallography, X-Ray↗
PubMed2005

Probing the pH-dependent structural features of alpha-KTx12.1, a potassium channel blocker from the scorpion Tityus serrulatus.

Potassium channels are widespread in living cells and are involved in many diseases. The scorpion toxin alpha-KTx(12.1) interacts with various K(+) channels, suggesting its capacity to match diverse channel pores. It is recognized that tissue injuries may affect the pH at toxins site of action, thereby modulating both protein conformation and activity. To better understand its molecular mechanism of action, we studied alpha-KTx(12.1) using pH as a tool to explore its plasticity and NMR in combination with MD calculations to detect it. The toxin solution structure consists of an alpha-helix and a triple-stranded beta-sheet stabilized by four disulfide bridges. The NMR results show, in addition, that His28 possesses an unusually low pK(a) of 5.2. The best set of protein conformers is obtained at pH 4.5, while at pH 7.0, the reduced number of NOEs resulting from a faster hydrogen exchange does not allow to reach a good structural convergence. Nonetheless, MD calculations show that the toxin structure does not vary significantly in that pH range, while conformational changes and modifications of the surface charge distribution occur when His28 is fully protonated. Moreover, essential dynamics analysis reveals variations in the toxin's coherent motions. In conclusion, His28, with its low pK(a) value, provides alpha-KTx(12.1) with the ability to preserve its active conformation over a wide pH interval, thus expanding the range of cellular conditions where the toxin can fully exhibit its activity. Overall, the results further underline the role of histidine as a natural controller of proteins' functionality.

Amino Acid Sequence↗
PubMed2003

Offspring size-number trade-offs in scorpions: an empirical test of the van Noordwijk and de Jong model.

Life-history traits are expected to exhibit negative phenotypic trade-offs, but often do not. In a seminal paper, van Noordwijk and de Jong (1986) provided an answer to this seeming paradox. According to their model, trade-offs will be more difficult to detect if variation in resource acquisition (or investment) is high relative to variation in resource allocation to the traits under consideration. Despite its influence on subsequent life-history studies, this model has rarely been tested. I use data from 10 species of scorpion (a total of 30 datasets, including multiple populations or years for some species) to test the van Noordwijk-de Jong model as modified to examine the relationship between offspring size and number. For both the overall data and a subset, including only the species Centruroides vittatus, I found that the correlation between offspring size and number within a population was significantly negatively correlated with the ratio of allocation variance to investment variance. That is, strong trade-offs were found when the investment variance was low relative to the allocation variance. These results were robust to the particular measure of offspring size and to whether offspring data were adjusted for female size variation. My results therefore provide strong evidence in support of the van Noordwijk and de Jong model.

Analysis of Variance↗
PubMed2006

Evolution of Mesobuthus gibbosus (Brullé, 1832) (Scorpiones: Buthidae) in the northeastern Mediterranean region.

Sequence data derived from two mitochondrial markers, 16S rRNA and COI genes, were used to infer the evolutionary history of 47 insular and mainland populations covering most of the distributional range of the northeastern Mediterranean scorpion species Mesobuthus gibbosus. Based on the estimated divergence times of Mesobuthus lineages, the temporal frame of the genus differentiation in the northeastern Mediterranean region is placed in middle Miocene (15 million years ago). The biogeographic affinities of M. gibbosus populations point towards a mainly vicariant pattern of differentiation of the species which is consistent with the geological events that transformed the Aegean region during the period from 12 to 5 million years ago. M. gibbosus is an old northeastern Mediterranean species that has retained valuable bits of genetic information, reflecting some of the oldest vicariant events that have occurred in the area. Most importantly, the history witnessed by M. gibbosus has not been obscured by more recent palaeoevents of the region. Therefore, the case of M. gibbosus is in favour of a taxon-oriented 'perception' of the natural history of a given area.

Animals↗
PubMed1983

Alpha-scorpion neurotoxin derivatives suitable as potential markers of sodium channels. Preparation and characterization.

Modified scorpion neurotoxins, i.e. mono-biotinylated and mono-azido derivatives either on lysine 58 or lysine 60 have been characterized both at the structural level (sequence and circular dichroism) and by their pharmacological activity (toxicity to mice and ability to displace 125I-Androctonus australis Hector toxin II from its receptor sites. The results allowed us to pinpoint a region of the molecule including lysine residues 58 and 60 that is important for neurotoxin receptor interaction. Furthermore, as these derivatives retain, after 125I labeling, high binding capacities to synaptosomal membranes, they can be used as potential labels of the sodium channel either by covalent binding or using the avidin-biotin system.

Animals↗