Conotoxin Phi-MiXXVIIA from the superfamily G2 employs a novel cysteine framework that mimics granulin and displays anti-apoptotic activity

Jin, Ai-Hua, Dekan, Zoltan, Smout, Michale J., Wilson, David, Dutertre, Sebastien, Vetter, Irina, Lewis, Richard J., Loukas, Alex, Daly, Norelle L., and Alewood, Paul F. (2017) Conotoxin Phi-MiXXVIIA from the superfamily G2 employs a novel cysteine framework that mimics granulin and displays anti-apoptotic activity. Angewandte Chemie International Edition, 56 (47). pp. 14973-14976.

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Abstract

Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Phi-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Phi-MiXXVIIA was determined by NMR spectroscopy. The 3D structure displays a unique topology containing two beta-hairpins that resemble the N-terminal domain of granulin. Similar to granulin, Phi-MiXXVIIA promotes cell proliferation (EC50 17.85 mu m) while inhibiting apoptosis (EC50 2.2 mu m). Additional frame-work XXVII sequences were discovered with homologous signal peptides that define the new conotoxin superfamily G2. The novel structure and biological activity of Phi-MiXXVIIA expands the repertoire of disulfide-rich conotoxins that recognize mammalian receptors.

Item ID: 51685
Item Type: Article (Research - C1)
ISSN: 1521-3773
Keywords: anti-apoptosis, conotoxins, cysteine, granulin, snail venom
Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC), National Institutes of Health (NIH)
Projects and Grants: ARC Future Fellowship FT110100226, NHMRC APP1072113, NIH R01CA164719
Date Deposited: 29 Nov 2017 07:42
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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