+ Translate
+ Most Popular
Spermatogenic and steroidogenic impairment after chromium treatment in rats
Prediction of enthalpy of formation based on refined crystal structures of multisite compounds; Part 1, Theories and examples
Intrastromal photorefractive keratectomy for myopia by Nd:YLF picosecond laser
Teachers' beliefs about the role of prior language knowledge in learning and how these influence teaching practices
Classification and genesis of submarine iron-manganese deposits
Insecta a Cl. G. N. Potanin in China et in Mongolia novissime lecta. XVII. Hemiptera-Heteroptera
On the occurrence of the splendid genus Machaerothrix Haupt in Tsushima, with some remarks on the genus (Hymenoptera, Pompilidae)
Enamel craze lines
Gynecologic examination of the child and the adolescent
Periosteal osteoclasts, skeletal development and ageing
Fibrodysplasia ossificans progressiva in a Nigerian: a case report
The chronically ill patient with anorexia nervosa development, phenomenology, and therapeutic considerations
Kummelonautilus taiwanum sp. nov. (Nautilida) from the early Miocene Shihmen Formation, Chungliao, Nantou, west-central Taiwan
Efficacy of Droncit against Dipylidium caninum in dogs
Pierids of the genus Euchloe Klots (Lepidoptera, Pieridae) from Siberia and the Far East.
C5A anaphylatoxin and its seven transmembrane-segment receptor
Failure to practice evidence-based medicine: why do physicians not treat patients with heart failure with angiotensin-converting enzyme inhibitors?
Empirical comparisons of proportional hazards regression, Poisson regression, and logistic regression in the analysis of occupational cohort data
Pollination of flowers of sweet and sour cherries
Isopodi terrestri raccolti nell' Estremo Oriente
Morphometric observations on Dipylidium caninum from dogs and cats in Austria
Chelation effectiveness of zinc proteinates demonstrated
Alopecia--a psychosomatic disease picture? I. Review of the literature
Monitoring equity in health and healthcare: a conceptual framework
Hemodynamic evaluation of the Biocor heterologous prosthesis

Common features in the functional surface of scorpion beta-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels

Common features in the functional surface of scorpion beta-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels

Journal of Biological Chemistry 280(6): 5045-5053

ISSN/ISBN: 0021-9258

PMID: 15569679

DOI: 10.1074/jbc.m408427200

Scorpion beta-toxins that affect the activation of mammalian voltage-gated sodium channels (Navs) have been studied extensively, but little is known about their functional surface and mode of interaction with the channel receptor. To enable a molecular approach to this question, we have established a successful expression system for the anti-mammalian scorpion beta-toxin, Css4, whose effects on rat brain Navs have been well characterized. A recombinant toxin, His-Css4, was obtained when fused to a His tag and a thrombin cleavage site and had similar binding affinity for and effect on Na currents of rat brain sodium channels as those of the native toxin isolated from the scorpion venom. Molecular dissection of His-Css4 elucidated a functional surface of 1245 A2 composed of the following: 1) a cluster of residues associated with the alpha-helix, which includes a putative "hot spot" (this cluster is conserved among scorpion beta-toxins and contains their "pharmacophore"); 2) a hydrophobic cluster associated mainly with the beta2 and beta3 strands, which is likely to confer the specificity for mammalian Navs; 3) a single bioactive residue (Trp-58) in the C-tail; and 4) a negatively charged residue (Glu-15) involved in voltage sensor trapping as inferred from our ability to uncouple toxin binding from activity upon its substitution. This study expands our understanding about the mode of action of scorpion beta-toxins and illuminates differences in the functional surfaces that may dictate their specificities for mammalian versus insect sodium channels.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 048587860

Download citation: RISBibTeXText

Related references

Mammalian skeletal muscle voltage-gated sodium channels are affected by scorpion depressant "insect-selective" toxins when preconditioned. Molecular Pharmacology 72(5): 1220-1227, 2007

Miniaturization of scorpion beta-toxins uncovers a putative ancestral surface of interaction with voltage-gated sodium channels. Journal of Biological Chemistry 283(22): 15169-15176, 2008

Australian funnel-web spider toxins and alpha-scorpion toxins share a common binding site on cockroach and rat voltage-gated sodium channels. Toxicon 36(9): 1273-1274, 1998

Scorpion beta-toxins and voltage-gated sodium channels: interactions and effects. Frontiers in Bioscience 18(2): 572-587, 2013

Dissection of the functional surface of an anti-insect excitatory toxin illuminates a putative "hot spot" common to all scorpion beta-toxins affecting Na+ channels. Journal of Biological Chemistry 279(9): 8206-8211, 2004

Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. Molecular Pharmacology 70(1): 340-347, 2006

Binding modes and functional surface of anti-mammalian scorpion α-toxins to sodium channels. Biochemistry 51(39): 7775-7782, 2012

Scorpion Toxins Targeting Voltage-gated Sodium Channels Associated with Pain. Current Pharmaceutical Biotechnology 19(11): 848-855, 2018

Molecular requirements for recognition of brain voltage-gated sodium channels by scorpion alpha-toxins. Journal of Biological Chemistry 284(31): 20684-20691, 2009

Structure-function map of the receptor site for β-scorpion toxins in domain II of voltage-gated sodium channels. Journal of Biological Chemistry 286(38): 33641-33651, 2011

The differential preference of scorpion -toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon 49(4): 452-472, 2007

The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon: Official Journal of the International Society on Toxinology 49(4): 452-472, 2007

Voltage sensitive sodium ion channels in mammalian peripheral nerves detected using scorpion toxins. Journal of Neurocytology 19(6): 851-872, 1990

A spider toxin that induces a typical effect of scorpion alpha-toxins but competes with beta-toxins on binding to insect sodium channels. Biochemistry 44(5): 1542-1549, 2005

Insect-selective spider toxins targeting voltage-gated sodium channels. Toxicon: Official Journal of the International Society on Toxinology 49(4): 490-512, 2007