Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins

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dc.contributor.author Wen, S
dc.contributor.author Wilson, DTR
dc.contributor.author Kuruppu, S
dc.contributor.author Korsinczky, MLJ
dc.contributor.author Hedrick, J
dc.contributor.author Pang, L
dc.contributor.author Szeto, T
dc.contributor.author Hodgson, WC
dc.contributor.author Alewood, PF
dc.contributor.author Nicholson, GM
dc.date.accessioned 2009-06-26T04:10:53Z
dc.date.issued 2005-12
dc.identifier.citation Peptides, 2005, 26 (12), pp. 2412 - 2426
dc.identifier.issn 0196-9781
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/593
dc.description.abstract 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 1 μM, 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 Ca 2+ 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 β-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. © 2005 Elsevier Inc. All rights reserved.
dc.language eng
dc.relation.hasversion Accepted manuscript version en_US
dc.relation.isbasedon 10.1016/j.peptides.2005.05.012
dc.title Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins
dc.title.alternative Discovery of an MIT-like atracotoxin family: spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins en_US
dc.type Journal Article
dc.description.version Published
dc.parent Peptides
dc.journal.volume 12
dc.journal.volume 26
dc.journal.number 12 en_US
dc.publocation New York, USA en_US
dc.identifier.startpage 2412 en_US
dc.identifier.endpage 2426 en_US
dc.cauo.name SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 1115 Pharmacology and Pharmaceutical Sciences
dc.personcode 870145
dc.personcode 010344
dc.percentage 100 en_US
dc.classification.name Pharmacology and Pharmaceutical Sciences en_US
dc.classification.type FOR-08 en_US
dc.custom 2.511 en_US
dc.description.keywords ACTX-Hvf17
dc.description.keywords Bv8
dc.description.keywords Funnel-web spider
dc.description.keywords Mamba intestinal toxin 1
dc.description.keywords Prokineticin
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:23:47.074767+10
pubs.consider-herdc true
utslib.collection.history General (ID: 2)
utslib.collection.history General Collection (ID: 346) [2015-05-15T14:11:13+10:00]


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