Openly accessible

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
Connect to link resolver
 
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
Citation counts: TR Web of Science Citation Count  Cited 24 times in TR Web of Science
Scopus Citation Count Cited 26 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 179 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.