A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily Ye, Mingyu, Khoo, Keith K., Xu, Shaoqiong, Zhou, Mi, Boonyalai, Nonlawat, Perugini, Matthew A, Shao, Xiaoxia, Chi, Chengwu, Galea, Charles A., Wang, Chunguang and Norton, Raymond S. 2012, A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily, Journal of biological chemistry, vol. 287, no. 18, pp. 14973-14983, doi: 10.1074/jbc.M111.334615. Attached Files Name Description MIMEType Size Downloads Title A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily Author(s) Ye, Mingyu Khoo, Keith K. Xu, Shaoqiong Zhou, Mi Boonyalai, Nonlawat Perugini, Matthew A Shao, Xiaoxia Chi, Chengwu Galea, Charles A. Wang, Chunguang Norton, Raymond S. Journal name Journal of biological chemistry Volume number 287 Issue number 18 Start page 14973 End page 14983 Total pages 11 Publisher American Society for Biochemistry and Molecular Biology Place of publication Manchester, Eng. Publication date 2012 ISSN 1083-351X Keyword(s) disulfide NMR peptides protein structure recombinant protein expression conotoxin cysteine framework superfamily Summary Cone snail venoms are a rich source of peptides, many of which are potent and selective modulators of ion channels and receptors. Here we report the isolation and characterization of two novel conotoxins from the venom of Conus imperialis. These two toxins contain a novel cysteine framework, C-C-C-CC-C, which has not been found in other conotoxins described to date. We name it framework XXIII and designate the two toxins im23a and im23b; cDNAs of these toxins exhibit a novel signal peptide sequence, which defines a new K-superfamily. The disulfide connectivity of im23a has been mapped by chemical mapping of partially reduced intermediates and by NMR structure calculations, both of which establish a I-II, III-IV, V-VI pattern of disulfide bridges. This pattern was also confirmed by synthesis of im23a with orthogonal protection of individual cysteine residues. The solution structure of im23a reveals that im23a adopts a novel helical hairpin fold. A cluster of acidic residues on the surface of the molecule is able to bind calcium. The biological activity of the native and recombinant peptides was tested by injection into mice intracranially and intravenously to assess the effects on the central and peripheral nervous systems, respectively. Intracranial injection of im23a or im23b into mice induced excitatory symptoms; however, the biological target of these new toxins has yet to be identified. Language eng DOI 10.1074/jbc.M111.334615 Field of Research 119999 Medical and Health Sciences not elsewhere classified Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category C1.1 Refereed article in a scholarly journal Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30063823 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)   Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Mon, 02 Jun 2014, 10:10:24 EST Mon, 02 Jun 2014, 11:33:28 EST Wed, 04 Mar 2015, 11:02:34 EST Sat, 09 Nov 2019, 09:42:21 EST Wed, 24 Feb 2021, 07:35:18 EST Filtered Full Citation counts:   Cited 24 times in TR Web of Science Cited 26 times in Scopus Search Google Scholar Access Statistics: 160 Abstract Views, 2 File Downloads  -  Detailed Statistics Created: Mon, 02 Jun 2014, 10:10:24 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.