DOCSLIB.ORG

Structural Venomics Reveals Evolution of a Complex Venom by Duplication and Diversification of an Ancient Peptide-Encoding Gene

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Structural Venomics Reveals Evolution of a Complex Venom by Duplication and Diversification of an Ancient Peptide-Encoding Gene Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene Sandy S. Pinedaa,b,1,2,3,4, Yanni K.-Y. China,c,1, Eivind A. B. Undheimc,d,e, Sebastian Senffa, Mehdi Moblic, Claire Daulyf, Pierre Escoubasg, Graham M. Nicholsonh, Quentin Kaasa, Shaodong Guoa, Volker Herziga,5, John S. Mattickb,6, and Glenn F. Kinga,2 aInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; bGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; cCentre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia; dCentre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway; eCentre for Ecological & Evolutionary Synthesis, Department of Biosciences, University of Oslo, 0316 Oslo, Norway; fThermo Fisher Scientific, 91941 Courtaboeuf Cedex, France; gUniversity of Nice Sophia Antipolis, 06000 Nice, France; and hSchool of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia Edited by Adriaan Bax, National Institutes of Health, Bethesda, MD, and approved March 18, 2020 (received for review August 21, 2019) Spiders are one of the most successful venomous animals, with N-terminal strand is sometimes present (12). The cystine knot more than 48,000 described species. Most spider venoms are comprises a “ring” formed by two disulfide bonds and the in- dominated by cysteine-rich peptides with a diverse range of phar- tervening sections of the peptide backbone, with a third disulfide macological activities. Some spider venoms contain thousands of piercing the ring to create a pseudoknot (11). This knot provides unique peptides, but little is known about the mechanisms used to generate such complex chemical arsenals. We used an integrated transcriptomic, proteomic, and structural biology approach to Significance demonstrate that the lethal Australian funnel-web spider pro- duces 33 superfamilies of venom peptides and proteins. Twenty- The venom of the Australian funnel-web spider is one of the six of the 33 superfamilies are disulfide-rich peptides, and we show most complex chemical arsenals in the natural world, com- BIOCHEMISTRY that 15 of these are knottins that contribute >90% of the venom prising thousands of peptide toxins. These toxins have a di- proteome. NMR analyses revealed that most of these disulfide-rich verse range of pharmacological activities and vary in size from peptides are structurally related and range in complexity from sim- short (3 to 4 kDa) to long (8 to 9 kDa). It is unclear how spiders ple to highly elaborated knottin domains, as well as double-knot evolved such complex venoms and whether there is an evolu- toxins, that likely evolved from a single ancestral toxin gene. tionary relationship between short and long toxins. Here, we introduce a “structural venomics” approach to show that the spider venom | venom evolution | structural venomics | transcriptomics | venom of Australian funnel-web spiders evolved primarily by proteomics duplication and elaboration of a single ancestral knottin gene; short toxins are simple knottins whereas most long toxins are piders evolved from an arachnid ancestor in the Late Or- either highly elaborated single-domain knottins or double-knot Sdovician around 450 million years ago (1), and they have toxins created by intragene duplications. since become one of the most successful animal lineages on the planet, with >100,000 extant species (2). A key contributor to Author contributions: S.S.P., E.A.B.U., J.S.M., and G.F.K. designed research; S.S.P., Y.K.-Y.C., E.A.B.U., S.S., M.M., C.D., P.E., G.M.N., Q.K., S.G., and V.H. performed research; their evolutionary success is the use of venom to capture prey S.S.P., Y.K.-Y.C., E.A.B.U., S.S., M.M., C.D., P.E., G.M.N., Q.K., S.G., V.H., and G.F.K. analyzed and defend against predators. The constant selection pressure on data; and S.S.P., Y.K.-Y.C., E.A.B.U., and G.F.K. wrote the paper. venoms over hundreds of millions of years has enabled them to Competing interest statement: C.D. is affiliated with Thermo Fisher Scientific. evolve into complex mixtures of bioactive compounds with a This article is a PNAS Direct Submission. diverse range of pharmacological activities. Published under the PNAS license. Spider venoms are a heterogeneous mixture of salts, low Data deposition: Atomic coordinates for protein structures determined in this study were molecular weight organic compounds (<1 kDa), linear and deposited in the Protein Data Bank under accession codes 2N6N, 2N6R, 6BA3, and 2N8K disulfide-rich peptides (DRPs) (typically, 3 to 9 kDa with three while corresponding NMR chemical shifts were deposited in BioMagResBank under to six disulfide bonds), and proteins (10 to 120 kDa) (3–5). accessions BMRB25774, BMRB25778, BMRB25853,andBMRB30352. Metadata and annotated nucleotide sequences were deposited in the European Nucleotide Archive However, peptides are the major components of most spider under project accessions PRJEB6062 (ERA298588)andPRJEB35693. Mass spectrometry venoms, with some containing >1,000 peptides (6). The majority data has been deposited to ProteomeXchange Consortium via the PRIDE partner of these peptides are “short” DRPs (2.5 to 5 kDa), but there is repository with the dataset identifier PXD016886. also a significant proportion of “long” DRPs (6.5 to 8.5 kDa) (5). 1S.S.P. and Y.K.-Y.C. contributed equally to the work. As the primary function of spider venom is to rapidly immobilize 2To whom correspondence may be addressed. Email: [email protected] or glenn. prey, it is perhaps not surprising that most spider-venom DRPs [email protected]. that have been functionally characterized target neuronal ion 3Present address: Brain and Mind Centre, University of Sydney, Camperdown, NSW 2050, channels and receptors (5, 7). Australia. 4 ’ Although spider-venom DRPs have been shown to adopt a Present address: St Vincent s Clinical School, University of New South Wales, Sydney, NSW 2010, Australia. variety of three-dimensional (3D) structures, including the 5 β Present address: School of Science & Engineering, University of the Sunshine Coast, Sippy Kunitz (8), prokineticin/colipase (9), disulfide-directed -hairpin Downs, QLD 4556, Australia. (DDH) (10), and inhibitor cystine knot (ICK) fold (11), the 6Present address: School of Biotechnology & Biomolecular Sciences, University of New majority of spider-venom DRP structures solved to date conform South Wales, Sydney, NSW 2010, Australia. to the ICK motif. The ICK motif is defined as an antiparallel This article contains supporting information online at https://www.pnas.org/lookup/suppl/ β-sheet stabilized by a cystine knot (11). In spider toxins, the doi:10.1073/pnas.1914536117/-/DCSupplemental. β-sheet typically comprises only two β-strands although a third First published May 12, 2020. www.pnas.org/cgi/doi/10.1073/pnas.1914536117 PNAS | May 26, 2020 | vol. 117 | no. 21 | 11399–11408 Downloaded by guest on September 25, 2021 ICK peptides (also known as knottins) (13) with exceptional The distribution of peptide masses in H. infensa venom is bi- resistance to chemicals, heat, and proteases (14, 15), which has modal. Most peptides fall in the mass range 2.5 to 5.5 kDa, but made them of interest as drug and insecticide leads (5, 14, 16). there is a significant cohort of larger peptides with mass 6.5 to Some spider toxins show minor (17) or more significant (18) 8.5 kDa (Fig. 1 C and D). This bimodal distribution matches that elaborations of the basic ICK fold involving an additional sta- previously described for venom from related funnel-web spiders bilizing disulfide bond. More recently, “double-knot” spider (6, 25), various tarantulas (26), and the spitting spider Scytodes toxins have been reported in which two structurally independent thoracica (27), and it is also reflected in the mass profile generated ICK domains are joined by a short linker (19, 20). for all spider toxins reported to date (5). As reported previously Like other folds with stabilizing disulfide bridges, knottins for Australian funnel-web spiders (6, 25), the 3D venom landscape display a remarkable diversity of biological functions, including (Fig. 1F) revealed no correlation between peptide mass and modulation of many different types of ligand- and voltage-gated peptide hydrophobicity, as judged by reversed-phase (RP) high- ion channels (5). Despite strong conservation of the knottin pressure liquid chromatography (HPLC) retention time. scaffold across a taxonomically diverse range of spiders, several factors have hampered analysis of their evolutionary history (21). Transcriptomics Uncovers the Biochemical Diversity of H. infensa First, it is not until recently that a large number of knottin pre- Venom. Consistent with MS analysis of secreted venom, se- cursor sequences have become available from venom-gland quencing of a venom-gland transcriptome from H. infensa transcriptomes. Second, the disulfide framework in small DRPs revealed a biochemically diverse venom, with at least 33 toxin generally constrains the peptide fold to such an extent that most superfamilies (Fig. 2). In light of their likely toxic function, each noncysteine residues can be mutated without damaging the pep- superfamily of toxins was named, as suggested previously (28), tide’s structural integrity, a luxury not afforded to most globular after gods/deities of death, destruction, or the underworld. proteins (21). Thus, evolution of DRPs is typically characterized Expressed sequence tags were sequenced using the 454 platform by the accumulation of many mutations, leaving very few con- and assembled using MIRA v3.2 (29). This produced a total of served residues available for deep evolutionary analyses (21). 26,980 contigs and 7,194 singlets, with an average contig length Third, very few structures have been solved for DRPs larger than 5 of 496 base pairs (bp) (maximum length 3,159 bp, N50 674 bp).
Load more

Recommended publications
  • Scorpion Toxins Targeted Against the Sarcoplasmic Reticulum Ca2+-Release Channel of Skeletal and Cardiac Muscle
    Proc. Nati. Acad. Sci. USA Vol. 89, pp. 12185-12189, December 1992 Physiology Scorpion toxins targeted against the sarcoplasmic reticulum Ca2+-release channel of skeletal and cardiac muscle (ryanodine receptors/Pandinus imperator venom/planar bilayer/ventricular myocytes/Ca2+ indicator) HECTOR H. VALDIVIA*t, MARK S. KIRBYf, W. JONATHAN LEDERER*, AND ROBERTO CORONADO*t *Department of Physiology, University of Wisconsin School of Medicine, Madison, WI 53706; and tDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Communicated by Michael V. L. Bennett, September 21, 1992 ABSTRACT We report the purification of two peptides, peratoxin inhibitor (IpTxi)] or activated [imperatoxin activa- called "imperatoxin inhibitor" and "imperatoxin activator," tor (IpTxa)] ryanodine receptors of skeletal and cardiac from the venom of the scorpion Pandinus imperator targeted muscle. Part of these results have been communicated in an against ryanodine receptor Ca2+-release channels. Impera- abstract form (8). toxin inhibitor has a Mr of 10,500, inhibits [3Hjryanodine binding to skeletal and cardiac sarcoplasmic reticulum with an EDso of 10 nM, and blocks openings of skeletal and cardiac EXPERIMENTAL PROCEDURES Ca2+-release channels incorporated into planar bilayers. In Purification of Scorpion Toxins. Lyophilized P. imperator whole-cell recordings of cardiac myocytes, imperatoxin inhib- venom was obtained from Latoxan (Rosans, France). Venom itor decreased twitch amplitude and intracellular Ca2+ tran- (50 mg per batch) was extracted in 2-3 ml of deionized water sients, suggesting a selective blockade of Ca2+ release from the and chromatographed on a column (1. 5 x 125 cm) of Sepha- sarcoplasmic reticulum. Imperatoxin activator has a Mr of dex G-50 fine.
    [Show full text]
  • Multiple Actions of Φ-LITX-Lw1a on Ryanodine Receptors Reveal a Functional Link Between Scorpion DDH and ICK Toxins
    Multiple actions of φ-LITX-Lw1a on ryanodine receptors reveal a functional link between scorpion DDH and ICK toxins Jennifer J. Smitha, Irina Vettera, Richard J. Lewisa, Steve Peigneurb, Jan Tytgatb, Alexander Lamc, Esther M. Gallantc, Nicole A. Beardd, Paul F. Alewooda,1,2, and Angela F. Dulhuntyc,1,2 aChemical and Structural Biology, Institute for Molecular Biosciences, University of Queensland, St. Lucia, QLD 4072, Australia; bLaboratory of Toxicology, University of Leuven, 3000 Leuven, Belgium; cDepartment of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia; and dDiscipline of Biomedical Sciences, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, ACT 2601, Australia Edited by Clara Franzini-Armstrong, University of Pennsylvania Medical Center, Philadelphia, PA, and approved April 23, 2013 (received for review August 26, 2012) We recently reported the isolation of a scorpion toxin named U1- mutations, atypical posttranslational modifications of RyRs, liotoxin-Lw1a (U1-LITX-Lw1a) that adopts an unusual 3D fold termed including hyperphosphorylation and S-nitrosylation, have been the disulfide-directed hairpin (DDH) motif, which is the proposed implicated in heart failure and pathologic muscle fatigue (10– evolutionary structural precursor of the three-disulfide-containing 12). Because of their wide distribution, there is mounting evidence inhibitor cystine knot (ICK) motif found widely in animals and plants. to suggest that dysregulation of RyRs also plays a role in a plethora Here we reveal that U1-LITX-Lw1a targets and activates the mam- of other disease states, including chronic pain, neurodegenerative malian ryanodine receptor intracellular calcium release channel (RyR) disorders such as Alzheimer’s disease, and intellectual deficit (13– with high (fM) potency and provides a functional link between DDH 15).
    [Show full text]
  • Final Project Completion Report
    CEPF SMALL GRANT FINAL PROJECT COMPLETION REPORT Organization Legal Name: - Tarantula (Araneae: Theraphosidae) spider diversity, distribution and habitat-use: A study on Protected Area adequacy and Project Title: conservation planning at a landscape level in the Western Ghats of Uttara Kannada district, Karnataka Date of Report: 18 August 2011 Dr. Manju Siliwal Wildlife Information Liaison Development Society Report Author and Contact 9-A, Lal Bahadur Colony, Near Bharathi Colony Information Peelamedu Coimbatore 641004 Tamil Nadu, India CEPF Region: The Western Ghats Region (Sahyadri-Konkan and Malnad-Kodugu Corridors). 2. Strategic Direction: To improve the conservation of globally threatened species of the Western Ghats through systematic conservation planning and action. The present project aimed to improve the conservation status of two globally threatened (Molur et al. 2008b, Siliwal et al., 2008b) ground dwelling theraphosid species, Thrigmopoeus insignis and T. truculentus endemic to the Western Ghats through systematic conservation planning and action. Investment Priority 2.1 Monitor and assess the conservation status of globally threatened species with an emphasis on lesser-known organisms such as reptiles and fish. The present project was focused on an ignored or lesser-known group of spiders called Tarantulas/ Theraphosid spiders and provided valuable information on population status and potential conservation sites in Uttara Kannada district, which will help in future monitoring and assessment of conservation status of the two globally threatened theraphosid species T. insignis and Near Threatened T. truculentus. Investment Priority 2.3. Evaluate the existing protected area network for adequate globally threatened species representation and assess effectiveness of protected area types in biodiversity conservation.
    [Show full text]
  • Structural Venomics Reveals Evolution of a Complex Venom by Duplication and Diversification of an Ancient Peptide-Encoding Gene
    Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene Sandy S. Pinedaa,b,1,2,3,4, Yanni K.-Y. China,c,1, Eivind A. B. Undheimc,d,e, Sebastian Senffa, Mehdi Moblic, Claire Daulyf, Pierre Escoubasg, Graham M. Nicholsonh, Quentin Kaasa, Shaodong Guoa, Volker Herziga,5, John S. Mattickb,6, and Glenn F. Kinga,2 aInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; bGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; cCentre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia; dCentre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway; eCentre for Ecological & Evolutionary Synthesis, Department of Biosciences, University of Oslo, 0316 Oslo, Norway; fThermo Fisher Scientific, 91941 Courtaboeuf Cedex, France; gUniversity of Nice Sophia Antipolis, 06000 Nice, France; and hSchool of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia Edited by Adriaan Bax, National Institutes of Health, Bethesda, MD, and approved March 18, 2020 (received for review August 21, 2019) Spiders are one of the most successful venomous animals, with N-terminal strand is sometimes present (12). The cystine knot more than 48,000 described species. Most spider venoms are comprises a “ring” formed by two disulfide bonds and the in- dominated by cysteine-rich peptides with a diverse range of phar- tervening sections of the peptide backbone, with a third disulfide macological activities. Some spider venoms contain thousands of piercing the ring to create a pseudoknot (11).
    [Show full text]
  • Maurocalcine-Derivatives As Biotechnological Tools for The
    Maurocalcine-derivatives as biotechnological tools for the penetration of cell-impermeable compounds Narendra Ram, Emilie Jaumain, Michel Ronjat, Fabienne Pirollet, Michel de Waard To cite this version: Narendra Ram, Emilie Jaumain, Michel Ronjat, Fabienne Pirollet, Michel de Waard. Maurocalcine- derivatives as biotechnological tools for the penetration of cell-impermeable compounds: Technological value of a scorpion toxin. de Lima, M.E.; de Castro Pimenta, A.M.; Martin-Eauclaire, M.F.; Bendeta Zengali, R.; Rochat, H. E. Animal Toxins: state of the art: Perspectives in Health and Biotechnology., Editora UFMG Belo Horizonte, Brazil, pp.715-732, 2009. inserm-00515224 HAL Id: inserm-00515224 https://www.hal.inserm.fr/inserm-00515224 Submitted on 5 Sep 2013 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Maurocalcine-derivatives as biotechnological tools for the penetration of cell-impermeable compounds by Narendra Ram1,2, Emilie Jaumain1,2, Michel Ronjat1,2, Fabienne Pirollet1,2 & Michel De Waard1,2* 1 INSERM, U836, Team 3: Calcium channels, functions and pathologies, BP 170, Grenoble Cedex 9, F-38042, France 2 Université Joseph Fourier, Institut des Neurosciences, BP 170, Grenoble Cedex 9, F-38042, France Running title: Technological value of a scorpion toxin *To whom correspondence should be sent: Dr.
    [Show full text]
  • Venom Week 2012 4Th International Scientific Symposium on All Things Venomous
    17th World Congress of the International Society on Toxinology Animal, Plant and Microbial Toxins & Venom Week 2012 4th International Scientific Symposium on All Things Venomous Honolulu, Hawaii, USA, July 8 – 13, 2012 1 Table of Contents Section Page Introduction 01 Scientific Organizing Committee 02 Local Organizing Committee / Sponsors / Co-Chairs 02 Welcome Messages 04 Governor’s Proclamation 08 Meeting Program 10 Sunday 13 Monday 15 Tuesday 20 Wednesday 26 Thursday 30 Friday 36 Poster Session I 41 Poster Session II 47 Supplemental program material 54 Additional Abstracts (#298 – #344) 61 International Society on Thrombosis & Haemostasis 99 2 Introduction Welcome to the 17th World Congress of the International Society on Toxinology (IST), held jointly with Venom Week 2012, 4th International Scientific Symposium on All Things Venomous, in Honolulu, Hawaii, USA, July 8 – 13, 2012. This is a supplement to the special issue of Toxicon. It contains the abstracts that were submitted too late for inclusion there, as well as a complete program agenda of the meeting, as well as other materials. At the time of this printing, we had 344 scientific abstracts scheduled for presentation and over 300 attendees from all over the planet. The World Congress of IST is held every three years, most recently in Recife, Brazil in March 2009. The IST World Congress is the primary international meeting bringing together scientists and physicians from around the world to discuss the most recent advances in the structure and function of natural toxins occurring in venomous animals, plants, or microorganisms, in medical, public health, and policy approaches to prevent or treat envenomations, and in the development of new toxin-derived drugs.
    [Show full text]
  • SA Spider Checklist
    REVIEW ZOOS' PRINT JOURNAL 22(2): 2551-2597 CHECKLIST OF SPIDERS (ARACHNIDA: ARANEAE) OF SOUTH ASIA INCLUDING THE 2006 UPDATE OF INDIAN SPIDER CHECKLIST Manju Siliwal 1 and Sanjay Molur 2,3 1,2 Wildlife Information & Liaison Development (WILD) Society, 3 Zoo Outreach Organisation (ZOO) 29-1, Bharathi Colony, Peelamedu, Coimbatore, Tamil Nadu 641004, India Email: 1 [email protected]; 3 [email protected] ABSTRACT Thesaurus, (Vol. 1) in 1734 (Smith, 2001). Most of the spiders After one year since publication of the Indian Checklist, this is described during the British period from South Asia were by an attempt to provide a comprehensive checklist of spiders of foreigners based on the specimens deposited in different South Asia with eight countries - Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. The European Museums. Indian checklist is also updated for 2006. The South Asian While the Indian checklist (Siliwal et al., 2005) is more spider list is also compiled following The World Spider Catalog accurate, the South Asian spider checklist is not critically by Platnick and other peer-reviewed publications since the last scrutinized due to lack of complete literature, but it gives an update. In total, 2299 species of spiders in 67 families have overview of species found in various South Asian countries, been reported from South Asia. There are 39 species included in this regions checklist that are not listed in the World Catalog gives the endemism of species and forms a basis for careful of Spiders. Taxonomic verification is recommended for 51 species. and participatory work by arachnologists in the region.
    [Show full text]
  • Cell Penetration Properties of a Highly Efficient Mini Maurocalcine Peptide
    Pharmaceuticals 2013, 6, 320-339; doi:10.3390/ph6030320 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Article Cell Penetration Properties of a Highly Efficient Mini Maurocalcine Peptide Céline Tisseyre 1,2,3,†, Eloi Bahembera 1,2,3,†, Lucie Dardevet 1,2,3, Jean-Marc Sabatier 4, Michel Ronjat 1,2,3 and Michel De Waard 1,2,4,5,* 1 Unité Inserm U836, Grenoble Institute of Neuroscience, Université Joseph Fourier, La Tronche, Chemin Fortuné Ferrini, Bâtiment Edmond Safra, 38042 Grenoble Cedex 09, France 2 Labex Ion Channel Science and Therapeutics, Nice, France 3 Université Joseph Fourier, Grenoble, France 4 Inserm U1097, Parc scientifique et technologique de Luminy, 163, avenue de Luminy, 13288 Marseille cedex 09, France 5 Smartox Biotechnology, Biopolis, 5 Avenue du Grand Sablon, 38700 La Tronche, France † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +33-4-56-52-05-63; Fax: +33-4-56-52-06-37. Received: 23 February 2013; in revised form: 6 March 2013 / Accepted: 7 March 2013 / Published: 18 March 2013 Abstract: Maurocalcine is a highly potent cell-penetrating peptide isolated from the Tunisian scorpion Maurus palmatus. Many cell-penetrating peptide analogues have been derived from the full-length maurocalcine by internal cysteine substitutions and sequence truncation. Herein we have further characterized the cell-penetrating properties of one such peptide, MCaUF1-9, whose sequence matches that of the hydrophobic face of maurocalcine. This peptide shows very favorable cell-penetration efficacy compared to Tat, penetratin or polyarginine.
    [Show full text]
  • Channel Toxin from Parabuthus Transvaalicus
    Eur. J. Biochem. 269, 5369–5376 (2002) Ó FEBS 2002 doi:10.1046/j.1432-1033.2002.03171.x A single charged surface residue modifies the activity of ikitoxin, a beta-type Na+ channel toxin from Parabuthus transvaalicus A. Bora Inceoglu1,*, Yuki Hayashida2, Jozsef Lango3, Andrew T. Ishida2 and Bruce D. Hammock1 1Department of Entomology and Cancer Research Center, 2Section of Neurobiology, Physiology and Behavior, and 3Department of Chemistry and Superfund Analytical Laboratory, University of California, Davis, CA, USA We previously purified and characterized a peptide toxin, from birtoxin by a single residue change from glycine to birtoxin, from the South African scorpion Parabuthus glutamic acid at position 23, consistent with the apparent transvaalicus. Birtoxin is a 58-residue, long chain neurotoxin mass difference of 72 Da. This single-residue difference that has a unique three disulfide-bridged structure. Here we renders ikitoxin much less effective in producing the same report the isolation and characterization of ikitoxin, a pep- behavioral effect as low concentrations of birtoxin. Elec- tide toxin with a single residue difference, and a markedly trophysiological measurements showed that birtoxin and reduced biological activity, from birtoxin. Bioassays on mice ikitoxin can be classified as beta group toxins for voltage- showed that high doses of ikitoxin induce unprovoked gated Na+ channels of central neurons. It is our conclusion jumps, whereas birtoxin induces jumps at a 1000-fold lower that the N-terminal loop preceding the a-helix in scorpion concentration. Both toxins are active against mice when toxins is one of the determinative domains in the interaction administered intracerebroventricularly.
    [Show full text]
  • Modulation of Neuropeptide Release Via Voltage-Dependent and -Independent Signaling in Isolated Neurohypophysial Terminals: a Dissertation
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2008-04-28 Modulation of Neuropeptide Release via Voltage-Dependent and -Independent Signaling in Isolated Neurohypophysial Terminals: a Dissertation Cristina M. Velazquez-Marrero University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Amino Acids, Peptides, and Proteins Commons, Biological Factors Commons, Chemical Actions and Uses Commons, Inorganic Chemicals Commons, and the Nervous System Commons Repository Citation Velazquez-Marrero CM. (2008). Modulation of Neuropeptide Release via Voltage-Dependent and -Independent Signaling in Isolated Neurohypophysial Terminals: a Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/tgm2-3725. Retrieved from https://escholarship.umassmed.edu/ gsbs_diss/367 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. MODULATION OF NEUROPEPTIDE RELEASE VIA VOLTAGE-DEPENDENT AND -INDEPENDENT SIGNALING IN ISOLATED NEUROHYPOPHYSIAL TERMINALS A Dissertation Presented By Cristina M. Velázquez-Marrero Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of: DOCTOR OF PHILOSOPHY April 28th, 2008 Neuroscience Copyright Notice ©Cristina M. Velazquez-Marrero All Rights Reserved ► C.M. Velázquez-Marrero, E.E. Custer, V. DeCrescenzo, R. Zhuge, J.V. Walsh, J.R. Lemos (2002). Caffeine stimulates basal neuropeptide release from nerve terminals of the neurohypophysis.
    [Show full text]
  • A Current Research Status on the Mesothelae and Mygalomorphae (Arachnida: Araneae) in Thailand
    A Current Research Status on the Mesothelae and Mygalomorphae (Arachnida: Araneae) in Thailand NATAPOT WARRIT Department of Biology Chulalongkorn University S piders • Globally included approximately 40,000+ described species (Platnick, 2008) • Estimated number 60,000-170,000 species (Coddington and Levi, 1991) S piders Spiders are the most diverse and abundant invertebrate predators in terrestrial ecosystems (Wise, 1993) SPIDER CLASSIFICATION Mygalomorphae • Mygalomorph spiders and Tarantulas Mesothelae • 16 families • 335 genera, 2,600 species • Segmented spider 6.5% • 1 family • 8 genera, 96 species 0.3% Araneomorphae • True spider • 95 families • 37,000 species 93.2% Mesothelae Liphistiidae First appeared during 300 MYA (96 spp., 8 genera) (Carboniferous period) Selden (1996) Liphistiinae (Liphistius) Heptathelinae (Ganthela, Heptathela, Qiongthela, Ryuthela, Sinothela, Songthela, Vinathela) Xu et al. (2015) 32 species have been recorded L. bristowei species-group L. birmanicus species-group L. trang species-group L. bristowei species-group L. birmanicus species-group L. trang species-group Schwendinger (1990) 5-7 August 2015 Liphistius maewongensis species novum Sivayyapram et al., Journal of Arachnology (in press) bristowei species group L. maewongensis L. bristowei L. yamasakii L. lannaianius L. marginatus Burrow Types Simple burrow T-shape burrow Relationships between nest parameters and spider morphology Trapdoor length (BL) Total length (TL) Total length = 0.424* Burrow length + 2.794 Fisher’s Exact-test S and M L Distribution
    [Show full text]
  • Download Article (PDF)
    OCCASIO AL PAPER NO. 239 ZOOLOGICAL SURVEY OF INDIA OCCASIONAL PAPERNO. 239 RECORDS OF THE ZOOLOGICAL SURVEY OF INDIA Arachnid fauna of Nallamalai Region, Eastern Ghats Andhra Pradesh, India K. THULSI RAO D.B. BASTAWADE* S.M. MAQSOOD JAVED I. SIVA RAMA'KRISHNA Assistant Conservator of Forests, Eco-Research & Monitoring Laboratories, Bio.diversity, Project TIger, Srisailanz-518 102. Kurnool Dist. Andhra Pradesh, India * Western Regional Station, Zoological Survey of India, Pune Edited by the Director, Zoological Survey of India, Kolkata Zoological S:~ey of India Kolkata CITATION Thulsi Rao, K., Bastawade, D.B., Maqsood Javed, S.M. and Siva Rama Krishna, I. 2005. Arachnid fauna of Nallamalai Region, Eastern Ghats, Andhra Pradesh, India, Rec. zool. Surv. India, Occ. Paper No. 239 : 1-42. (Published by the Director, zool Surv. India, Kolkata). Published: July, 2005 ISBN: 81-8171-075-4 © Government of India, 2005 ALL RIGHTS RESERVED • No part of this publication may be reprcduced, stored in a retrieval system or transmitted, in any from or by ~ny means, electronic, mechanical, photocopying, recording or otherwise without the prior permission of the publisher. • This book is sold subject to the condition that it shall .not, by way of trade, be lent, re-sold hired out or otherwise disposed of without the publisher's consent, in any form of binding or cover other than that in which it is published. • The correct price of this publication is the price printed on this page. Any revised price indicated by a rubber stamp or by a sticker or by any other means is incorrect and should be unacceptable.
    [Show full text]