Abstract
Cone snails comprise approximately 700 species of venomous molluscs which have evolved the ability to generate multiple toxins with varied and exquisite selectivity. α-Conotoxin is a powerful tool for defining the composition and function of nicotinic acetylcholine receptors which play a crucial role in excitatory neurotransmission and are important targets for drugs and insecticides. An α4/7 conotoxin, Lp1.1, originally identified by cDNA and genomic DNA cloning from Conus leopardus, was found devoid of the highly conserved Pro residue in the first intercysteine loop. To further study this toxin, α-Lp1.1 was chemically synthesized and refolded into its globular disulfide isomer. The synthetic Lp1.1 induced seizure and paralysis on freshwater goldfish and selectively reversibly inhibited ACh-evoked currents in Xenopus oocytes expressing rat α3β2 and α6α3β2 nAChRs. Comparing the distinct primary structure with other functionally related α-conotoxins could indicate structural features in Lp1.1 that may be associated with its unique receptor recognition profile.
Original language | English (US) |
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Pages (from-to) | 1700-1707 |
Number of pages | 8 |
Journal | Peptides |
Volume | 29 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2008 |
Externally published | Yes |
Keywords
- Conus
- Neuronal nicotinic acetylcholine receptor subtypes
- Xenopus oocytes
- α-Conotoxins
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Endocrinology
- Cellular and Molecular Neuroscience