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David Wilson - One of the best experts on this subject based on the ideXlab platform.
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variation in venom composition in the australian funnel web spiders Hadronyche valida
Toxicon: X, 2020Co-Authors: Linda Hernandez C Duran, Tasmin L Rymer, David WilsonAbstract:Mygalomorph venom properties and active components, which have importance in medicine, agronomy, venomics, ecology and evolution, have been widely studied, but only a small fraction have been characterised. Several studies have shown inter-individual variation in the composition of venom peptides based on ontogeny, sexual dimorphism, season and diet. However, intra-individual variation in venom composition, which could play a key role in the evolution, diversification and function of toxins, is poorly understood. In this study, we demonstrate significant intra- and inter-individual variation in venom composition in the Australian funnel-web spider Hadronyche valida, highlighting that individuals show different venom profiles over time. Fourteen (four juvenile and ten adult females) funnel-web spiders, maintained under the same environmental conditions and diet, were milked a total of four times, one month apart. We then used reversed-phase high performance liquid chromatography/electrospray ionisation mass spectrometry to generate venom fingerprints containing the retention time and molecular weights of the different toxin components in the venom. Across all individuals, we documented a combined total of 83 individual venom components. Only 20% of these components were shared between individuals. Individuals showed variation in the composition of venom peptides, with some components consistently present over time, while others were only present at specific times. When individuals were grouped using the Jaccard clustering index and Kernel Principal Component Analysis, spiders formed two distinct clusters, most likely due to their origin or time of collection. This study contributes to the understanding of variation in venom composition at different levels (intra-individual, and intra- and inter-specific) and considers some of the mechanisms of selection that may contribute to venom diversification within arachnids. In addition, inter-specific variation in venom composition can be highly useful as a chemotaxonomic marker to identify funnel-web species.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry
Journal of Proteomics, 2013Co-Authors: Alexandre Palagi, David Wilson, Jennifer Koh, Mathieu Leblanc, Sébastien Dutertre, Glenn King, Graham Nicholson, Pierre Escoubas, Jennifer M.s. KohAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~800 peptides in female venoms while male venoms contained ~400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400m/z range and to a lesser extent the 6600-8200m/z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules.
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Primary and tertiary structure of δ-hexatoxins.
2013Co-Authors: Sandy Steffany Pineda, David Wilson, John S. Mattick, Glenn F. KingAbstract:(A) Alignment of the amino acid sequences of the lethal toxins δ-hexatoxin-Hv1a (and its paralog δ-hexatoxin-Hv1b), δ-hexatoxin-Ar1a, δ-hexatoxin-Hi1a, and δ-hexatoxin-Iw1a from the Australian funnel-web spiders Hadronyche versuta, Atrax robustus, Hadronyche infensa, and Illawarra wisharti, respectively. Identical amino acids are boxed in black and conservative substitutions are shaded grey. (B) Ribbon representation of the three-dimensional structure of δ-hexatoxin-Hv1a (PDB code 1VTX) [26]. β-Strands and 310-helix are shown in orange and blue, respectively. The N- and C-termini are labeled. The three disulfide bonds shown in green form an inhibitor cystine knot motif while the disulfide bridge that connects the C-terminal Cys residue to the core ICK region is colored red.
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Discovery of an MIT-like atracotoxin family: spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins.
Peptides, 2005Co-Authors: Suping Wen, Paul Francis Alewood, David Wilson, Wayne C. Hodgson, Sanjaya Kuruppu, Michael L. J. Korsinczky, Joseph A. Hedrick, Ling Pang, Tim H. Szeto, Graham M. NicholsonAbstract:This project identified a novel family of six 66-68 residue peptides from the venom of two Australian funnel-web spiders, Hadronyche sp. 20 and H. infensa: Orchid Beach (Hexathelidae: Atracinae), that appear to undergo N- and/or C-terminal post-translational modifications and conform to an ancestral protein fold. These peptides all show significant amino acid sequence homology to atracotoxin-Hvf17 (ACTX-Hvf17), a non-toxic peptide isolated from the venom of H. versuta, and a variety of AVIT family proteins including mamba intestinal toxin 1 (MIT1) and its mammalian and piscine orthologs prokineticin 1 (PK1) and prokineticin 2 (PK2). These AVIT family proteins target prokineticin receptors involved in the sensitization of nociceptors and gastrointestinal smooth muscle activation. Given their sequence homology to MIT1, we have named these spider venom peptides the MIT-like atracotoxin (ACTX) family. Using isolated rat stomach fundus or guinea-pig ileum organ bath preparations we have shown that the prototypical ACTX-Hvf17, at concentrations up to 1muM, did not stimulate smooth muscle contractility, nor did it inhibit contractions induced by human PK1 (hPK1). The peptide also lacked activity on other isolated smooth muscle preparations including rat aorta. Furthermore, a FLIPR Ca2+ flux assay using HEK293 cells expressing prokineticin receptors showed that ACTX-Hvf17 fails to activate or block hPK1 or hPK2 receptors. Therefore, while the MIT-like ACTX family appears to adopt the ancestral disulfide-directed beta-hairpin protein fold of MIT1, a motif believed to be shared by other AVIT family peptides, variations in the amino acid sequence and surface charge result in a loss of activity on prokineticin receptors.
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solution structures of the cis and trans pro30 isomers of a novel 38 residue toxin from the venom of Hadronyche infensa sp that contains a cystine knot motif within its four disulfide bonds
Biochemistry, 2002Co-Authors: Johan K Rosengren, Norelle L Daly, Paul Francis Alewood, David Wilson, David J. CraikAbstract:The primary sequence and three-dimensional structure of a novel peptide toxin isolated from the Australian funnel-web spider Hadronyche infensa sp. is reported. ACTX-Hi:OB4219 contains 38 amino acids, including eight-cysteine residues that form four disulfide bonds. The connectivities of these disulfide bonds were previously unknown but have been unambiguously determined in this study. Three of these disulfide bonds are arranged in an inhibitor cystine-knot (ICK) motif, which is observed in a range of other disulfide-rich peptide toxins. The motif incorporates an embedded ring in the structure formed by two of the disulfides and their connecting backbone segments penetrated by a third disulfide bond. Using NMR spectroscopy, we determined that despite the isolation of a single native homologous product by RP-HPLC, ACTX-Hi:OB4219 possesses two equally populated conformers in solution. These two conformers were determined to arise from cis/trans isomerization of the bond preceding Pro30. Full assignment of t...
Glenn F. King - One of the best experts on this subject based on the ideXlab platform.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry.
Journal of proteomics, 2013Co-Authors: Alexandre Palagi, Glenn F. King, Mathieu Leblanc, Sébastien Dutertre, Jennifer M.s. Koh, Denise Wilson, Pierre EscoubasAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~. 43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~. 800 peptides in female venoms while male venoms contained ~. 400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400. m/. z range and to a lesser extent the 6600-8200. m/. z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. Biological significance: In the present study we describe the complexity of 18 venoms from lethal Australian funnel-web spiders using LC-MALDI-TOF MS. The study includes an in-depth investigation, focusing on four venoms, that revealed the presence of ~. 800 peptides in female venoms and ~. 400 peptides in male venoms. This is significantly higher than previous estimates of peptide expression in spider venoms. By constructing both 3D and 2D contour plots we were also able to reveal the distinct intersexual as well as intra- and inter-species variation in venom peptide masses. We show that peptide mass distributions in all 18 venoms were centered around the 3200-5400 m/. z range and to a lesser extent the 6600-8200 m/. z range, consistent with the small number of previously described hexatoxins from these spiders. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. The present study has greatly expanded our understanding of peptide variety and complexity in these lethal mygalomorph spiders. Specifically it highlights both the utility of LC-MALDI-TOF in spider taxonomy and the massive combinatorial peptide libraries that spider venoms offer the pharmaceutical and agrochemical industry.
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Primary and tertiary structure of δ-hexatoxins.
2013Co-Authors: Sandy Steffany Pineda, David Wilson, John S. Mattick, Glenn F. KingAbstract:(A) Alignment of the amino acid sequences of the lethal toxins δ-hexatoxin-Hv1a (and its paralog δ-hexatoxin-Hv1b), δ-hexatoxin-Ar1a, δ-hexatoxin-Hi1a, and δ-hexatoxin-Iw1a from the Australian funnel-web spiders Hadronyche versuta, Atrax robustus, Hadronyche infensa, and Illawarra wisharti, respectively. Identical amino acids are boxed in black and conservative substitutions are shaded grey. (B) Ribbon representation of the three-dimensional structure of δ-hexatoxin-Hv1a (PDB code 1VTX) [26]. β-Strands and 310-helix are shown in orange and blue, respectively. The N- and C-termini are labeled. The three disulfide bonds shown in green form an inhibitor cystine knot motif while the disulfide bridge that connects the C-terminal Cys residue to the core ICK region is colored red.
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The Lethal Toxin from Australian Funnel-Web Spiders Is Encoded by an Intronless Gene
2012Co-Authors: Steffany Y Pineda, John S. Mattick¤b, Glenn F. KingAbstract:Australian funnel-web spiders are generally considered the most dangerous spiders in the world, with envenomations from the Sydney funnel-web spider Atrax robustus resulting in at least 14 human fatalities prior to the introduction of an effective anti-venom in 1980. The clinical envenomation syndrome resulting from bites by Australian funnel-web spiders is due to a single 42-residue peptide known as d-hexatoxin. This peptide delays the inactivation of voltage-gated sodium channels, which results in spontaneous repetitive firing and prolongation of action potentials, thereby causing massive neurotransmitter release from both somatic and autonomic nerve endings. Here we show that d-hexatoxin from the Australian funnel-web spider Hadronyche versuta is produced from an intronless gene that encodes a prepropeptide that is post-translationally processed to yield the mature toxin. A limited sampling of genes encoding unrelated venom peptides from this spider indicated that they are all intronless. Thus, in distinct contrast to cone snails and scorpions, whose toxi
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orally active acaricidal peptide toxins from spider venom
Toxicon, 2006Co-Authors: Ashis K Mukherjee, Brianna L Sollod, Stephen K Wikel, Glenn F. KingAbstract:Numerous species of ticks and mites (collectively known as acarines) are serious pests of animals, humans, and crops. There are few commercially available acaricides and major classes of these chemicals continue to be lost from the marketplace due to resistance development or deregistration by regulatory agencies. There is consequently a pressing need to isolate new and safe acaricidal compounds. In this study, we show that two families of peptide neurotoxins isolated from the venom of the Australian funnel-web spider Hadronyche versuta are lethal to the lone star tick Amblyomma americanum. These toxins, which are specific blockers of arthropod voltage-gated calcium channels, induce a pronounced phenotype characterized by an unusual gait that is rapidly followed by paralysis and death. Remarkably, one of these toxins, the calcium channel blocker ω-atracotoxin-Hv1a, is virtually equipotent whether the toxin is injected or fed to A. americanum.
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isolation of a funnel web spider polypeptide with homology to mamba intestinal toxin 1 and the embryonic head inducer dickkopf 1
Toxicon, 2000Co-Authors: Tim H. Szeto, Graham M. Nicholson, Ross Smith, Mark Connor, Macdonald J. Christie, Xiuhong Wang, Glenn F. KingAbstract:We have isolated and determined the amino acid sequence of a novel peptide component from the venom of the Australian funnel-web spider Hadronyche versuta. This 68-residue toxin, ACTX-Hvf17, does not function like classical neurotoxins in modulating ion channel function as evidenced by its lack of insecticidal activity and its inability to affect vertebrate smooth or skeletal muscle contractility. The peptide shows significant sequence homology with mamba intestinal toxin 1 (MIT1) and to a lesser extent with a variety of colipases. The strong structural homology between MIT1 and porcine colipase leads us to propose that ACTX-Hvf17 also adopts the MIT1/colipase three-dimensional fold. However, we show that ACTX-Hvf17 has no colipase activity and does not stimulate muscle contractility like MIT1. We also show that MIT1 and ACTX-Hvf17 display significant sequence homology with the C-terminal cysteine-rich domain of the Dickkopf-1 family of proteins that induce head formation in developing embryos, which leads us to propose that this domain of Dickkopf-1 also adopts the MIT1/colipase fold. (C) 1999 Elsevier Science Ltd. All rights reserved.
Pierre Escoubas - One of the best experts on this subject based on the ideXlab platform.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry
Journal of Proteomics, 2013Co-Authors: Alexandre Palagi, David Wilson, Jennifer Koh, Mathieu Leblanc, Sébastien Dutertre, Glenn King, Graham Nicholson, Pierre Escoubas, Jennifer M.s. KohAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~800 peptides in female venoms while male venoms contained ~400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400m/z range and to a lesser extent the 6600-8200m/z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry.
Journal of proteomics, 2013Co-Authors: Alexandre Palagi, Glenn F. King, Mathieu Leblanc, Sébastien Dutertre, Jennifer M.s. Koh, Denise Wilson, Pierre EscoubasAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~. 43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~. 800 peptides in female venoms while male venoms contained ~. 400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400. m/. z range and to a lesser extent the 6600-8200. m/. z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. Biological significance: In the present study we describe the complexity of 18 venoms from lethal Australian funnel-web spiders using LC-MALDI-TOF MS. The study includes an in-depth investigation, focusing on four venoms, that revealed the presence of ~. 800 peptides in female venoms and ~. 400 peptides in male venoms. This is significantly higher than previous estimates of peptide expression in spider venoms. By constructing both 3D and 2D contour plots we were also able to reveal the distinct intersexual as well as intra- and inter-species variation in venom peptide masses. We show that peptide mass distributions in all 18 venoms were centered around the 3200-5400 m/. z range and to a lesser extent the 6600-8200 m/. z range, consistent with the small number of previously described hexatoxins from these spiders. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. The present study has greatly expanded our understanding of peptide variety and complexity in these lethal mygalomorph spiders. Specifically it highlights both the utility of LC-MALDI-TOF in spider taxonomy and the massive combinatorial peptide libraries that spider venoms offer the pharmaceutical and agrochemical industry.
Jennifer M.s. Koh - One of the best experts on this subject based on the ideXlab platform.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry
Journal of Proteomics, 2013Co-Authors: Alexandre Palagi, David Wilson, Jennifer Koh, Mathieu Leblanc, Sébastien Dutertre, Glenn King, Graham Nicholson, Pierre Escoubas, Jennifer M.s. KohAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~800 peptides in female venoms while male venoms contained ~400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400m/z range and to a lesser extent the 6600-8200m/z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry.
Journal of proteomics, 2013Co-Authors: Alexandre Palagi, Glenn F. King, Mathieu Leblanc, Sébastien Dutertre, Jennifer M.s. Koh, Denise Wilson, Pierre EscoubasAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~. 43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~. 800 peptides in female venoms while male venoms contained ~. 400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400. m/. z range and to a lesser extent the 6600-8200. m/. z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. Biological significance: In the present study we describe the complexity of 18 venoms from lethal Australian funnel-web spiders using LC-MALDI-TOF MS. The study includes an in-depth investigation, focusing on four venoms, that revealed the presence of ~. 800 peptides in female venoms and ~. 400 peptides in male venoms. This is significantly higher than previous estimates of peptide expression in spider venoms. By constructing both 3D and 2D contour plots we were also able to reveal the distinct intersexual as well as intra- and inter-species variation in venom peptide masses. We show that peptide mass distributions in all 18 venoms were centered around the 3200-5400 m/. z range and to a lesser extent the 6600-8200 m/. z range, consistent with the small number of previously described hexatoxins from these spiders. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. The present study has greatly expanded our understanding of peptide variety and complexity in these lethal mygalomorph spiders. Specifically it highlights both the utility of LC-MALDI-TOF in spider taxonomy and the massive combinatorial peptide libraries that spider venoms offer the pharmaceutical and agrochemical industry.
Alexandre Palagi - One of the best experts on this subject based on the ideXlab platform.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry
Journal of Proteomics, 2013Co-Authors: Alexandre Palagi, David Wilson, Jennifer Koh, Mathieu Leblanc, Sébastien Dutertre, Glenn King, Graham Nicholson, Pierre Escoubas, Jennifer M.s. KohAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~800 peptides in female venoms while male venoms contained ~400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400m/z range and to a lesser extent the 6600-8200m/z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules.
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Unravelling the complex venom landscapes of lethal Australian funnel-web spiders (Hexathelidae: Atracinae) using LC-MALDI-TOF mass spectrometry.
Journal of proteomics, 2013Co-Authors: Alexandre Palagi, Glenn F. King, Mathieu Leblanc, Sébastien Dutertre, Jennifer M.s. Koh, Denise Wilson, Pierre EscoubasAbstract:Spider venoms represent vast sources of bioactive molecules whose diversity remains largely unknown. Indeed, only a small subset of species have been studied out of the ~. 43,000 extant spider species. The present study investigated inter- and intra-species venom complexity in 18 samples collected from a variety of lethal Australian funnel-web spiders (Mygalomorphae: Hexathelidae: Atracinae) using C4 reversed-phase separation coupled to offline MALDI-TOF mass spectrometry (LC-MALDI-TOF MS). An in-depth investigation focusing on four atracine venoms (male Illawarra wisharti, male and female Hadronyche cerberea, and female Hadronyche infensa Toowoomba) revealed, on average, ~. 800 peptides in female venoms while male venoms contained ~. 400 peptides, distributed across most HPLC fractions. This is significantly higher than previous estimates of peptide expression in mygalomorph venoms. These venoms also showed distinct intersexual as well as intra- and inter-species variation in peptide masses. Construction of both 3D and 2D contour plots revealed that peptide mass distributions in all 18 venoms were centered around the 3200-5400. m/. z range and to a lesser extent the 6600-8200. m/. z range, consistent with previously described hexatoxins. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. Biological significance: In the present study we describe the complexity of 18 venoms from lethal Australian funnel-web spiders using LC-MALDI-TOF MS. The study includes an in-depth investigation, focusing on four venoms, that revealed the presence of ~. 800 peptides in female venoms and ~. 400 peptides in male venoms. This is significantly higher than previous estimates of peptide expression in spider venoms. By constructing both 3D and 2D contour plots we were also able to reveal the distinct intersexual as well as intra- and inter-species variation in venom peptide masses. We show that peptide mass distributions in all 18 venoms were centered around the 3200-5400 m/. z range and to a lesser extent the 6600-8200 m/. z range, consistent with the small number of previously described hexatoxins from these spiders. These findings highlight the extensive diversity of peptide toxins in Australian funnel-web spider venoms that that can be exploited as novel therapeutic and biopesticide lead molecules. The present study has greatly expanded our understanding of peptide variety and complexity in these lethal mygalomorph spiders. Specifically it highlights both the utility of LC-MALDI-TOF in spider taxonomy and the massive combinatorial peptide libraries that spider venoms offer the pharmaceutical and agrochemical industry.
