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Genève, Switzerland

Kuhn-Nentwig L.,University of Bern | Stocklin R.,Atheris Laboratories | Nentwig W.,University of Bern
Advances in Insect Physiology | Year: 2011

This review on all spider venom components known by the end of 2010 bases on 1618 records for venom compounds from 174 spider species (= 0.41% of all known species) belonging to 32 families (= 29% of all existing spider families). Spiders investigated for venom research are either big (many mygalomorph species, Nephilidae, Ctenidae and Sparassidae) or medically important for humans (e.g. Loxosceles or Latrodectus species). Venom research widely ignored so far the two most species-rich families (Salticidae and Linyphiidae) and strongly neglected several other very abundant families (Araneidae, Lycosidae, Theridiidae, Thomisidae and Gnaphosidae).We grouped the known 1618 records for venom compounds into six categories: low molecular mass compounds (16 % of all compounds), acylpolyamines (11 %), linear peptides (6 %), cysteine-knotted mini-proteins (60 %), neurotoxic proteins (1 %) and enzymes (6 %). Low molecular mass compounds are known from many spider families and contain organic acids, nucleosides, nucleotides, amino acids, amines, polyamines, and some further substances, many of them acting as neurotransmitters. Acylpolyamines contain amino acids (Araneidae and Nephilidae) or not (several other families) and show a very high diversity within one species. Linear peptides, also called cytolytic, membranolytic or antimicrobial, exert a highly specific structure and are so far only known from Ctenidae, Lycosidae, Oxyopidae and Zodariidae. Cysteine-knotted mini-proteins represent the majority of venom compounds because research so far focused on them. They probably occur in most but not all spider families. Neurotoxic proteins so far are only known from theridiid spiders. Enzymes had been neglected for some time but meanwhile it becomes obvious that they play an important role in spider venoms. Sixteen enzymes either cleave polymers in the extracellular matrix or target phospholipids and related compounds in membranes. The overall structure of these compounds is given and the function, as far as it is known, is described. Since several of these component groups are presented in one average spider venom, we discuss the known interactions and synergisms and give reasons for such a functional redundancy. We also discuss main evolutionary pathways for spider venom compounds such as high variability among components of one group, synergistic interactions between cysteine-knotted mini-proteins and other components (low molecular mass compounds and linear peptides), change of function from ion-channel acting mini-proteins to cytolytic effects and replacement of mini-proteins by linear peptides, acylpolyamines, large proteins or enzymes. We also add first phylogenetic considerations. © 2011 Elsevier Ltd. Source

Coissac E.,CNRS Alpine Ecology Laboratory | Riaz T.,CNRS Alpine Ecology Laboratory | Puillandre N.,Atheris Laboratories | Puillandre N.,French Natural History Museum
Molecular Ecology | Year: 2012

Almost all empirical studies in ecology have to identify the species involved in the ecological process under examination. DNA metabarcoding, which couples the principles of DNA barcoding with next generation sequencing technology, provides an opportunity to easily produce large amounts of data on biodiversity. Microbiologists have long used metabarcoding approaches, but use of this technique in the assessment of biodiversity in plant and animal communities is under-explored. Despite its relationship with DNA barcoding, several unique features of DNA metabarcoding justify the development of specific data analysis methodologies. In this review, we describe the bioinformatics tools available for DNA metabarcoding of plants and animals, and we revisit others developed for DNA barcoding or microbial metabarcoding. We also discuss the principles and associated tools for evaluating and comparing DNA barcodes in the context of DNA metabarcoding, for designing new custom-made barcodes adapted to specific ecological question, for dealing with PCR and sequencing errors, and for inferring taxonomical data from sequences. © 2012 Blackwell Publishing Ltd. Source

Ligutti J.,Neuroscience | Liu D.,Neuroscience | Zou A.,Neuroscience | Li H.,Amgen Inc. | And 4 more authors.
Journal of Medicinal Chemistry | Year: 2015

NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp29, Lys31, and Phe34 near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5. © 2015 American Chemical Society. Source

Leonardi A.,Jozef Stefan Institute | Biass D.,Atheris Laboratories | Kordis D.,Jozef Stefan Institute | Stocklin R.,Atheris Laboratories | And 3 more authors.
Journal of Proteome Research | Year: 2012

For some decades, cone snail venoms have been providing peptides, generally termed conopeptides, that exhibit a large diversity of pharmacological properties. However, little attention has been devoted to the high molecular mass (HMM) proteins in venoms of mollusks. In order to shed more light on cone snail venom HMM components, the proteins of dissected and injected venom of a fish-hunting cone snail, Conus consors, were extensively assessed. HMM venom proteins were separated by two-dimensional polyacrylamide gel electrophoresis and analyzed by mass spectrometry (MS). The MS data were interpreted using UniProt database, EST libraries from C. consors venom duct and salivary gland, and their genomic information. Numerous protein families were discovered in the lumen of the venom duct and assigned a biological function, thus pointing to their potential role in venom production and maturation. Interestingly, the study also revealed original proteins defining new families of unknown function. Only two groups of HMM proteins passing the venom selection process, echotoxins and hyaluronidases, were clearly present in the injected venom. They are suggested to contribute to the envenomation process. This newly devised integrated HMM proteomic analysis is a big step toward identification of the protein arsenal used in a cone snail venom apparatus for venom production, maturation, and function. © 2012 American Chemical Society. Source

Eugster P.J.,University of Geneva | Biass D.,Atheris Laboratories | Guillarme D.,University of Geneva | Favreau P.,Atheris Laboratories | And 2 more authors.
Journal of Chromatography A | Year: 2012

The high resolution profiling of complex mixtures is indispensable for obtaining online structural information on the highest possible number of the analytes present. This is particularly relevant for natural extracts, as for the venom of the predatory marine snail Conus consors, which contains numerous bioactive peptides with molecular masses ranging between 1000 and 5000. Da. The goal of the present work was to maximise peak capacity of peptides separations by LC-MS while maintaining a reasonable analysis time. The best gradient performance using the C. consors venom as a real sample was obtained with a mobile phase flow rate as high as possible to maximise performance in the gradient mode, and gradient time comprised between 75 and 350. min when using a 150 mm column length. The present study also confirmed that an elevated temperature (up to 90. °C) improves performance under ultra-high pressure liquid chromatography (UHPLC) conditions. However, the thermal stability of the analytes had to be critically evaluated. For the profiling of C. consors, analyte degradation was not clearly observable at 90. °C with analysis times of approximately 100. min. Finally, the MS source was found to cause significant additional band broadening in the UHPLC mode (σext2 was 10-24 times higher using TOF-MS vs. UV detection). Thus, if the MS contributes strongly to the peak capacity loss, classical 2.1 mm I.D. columns can be replaced by 3.0 mm I.D. to mitigate this problem. Based on these considerations, the optimal generic profiling conditions applied to the C. consors venom provided a peak capacity higher than 1100 for a gradient time of around 100. min, doubling the values reached by classical HPLC separation. UHPLC-QTOF-MS/MS experiments carried out in these conditions provided exploitable data that matched with peptides present in the C. consors venom. These optimal LC conditions are thus compatible with online peptide deconvolution and matching against transcriptomic data and, to some extent, de novo sequencing in such complex mixtures. © 2012 Elsevier B.V. Source

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