Conotoxin
This article is missing information about genetic and architectural classification (ConoServer and PMC4278219).(April 2019) |
Alpha conotoxin precursor | |||||||||
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OPM superfamily | 148 | ||||||||
OPM protein | 1akg | ||||||||
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Omega conotoxin | |||||||||
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OPM superfamily | 112 | ||||||||
OPM protein | 1fyg | ||||||||
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A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.
Conotoxins, which are peptides consisting of 10 to 30
The LD50 of conotoxin ranges from 5-25 μg/kg.[3][4][5]
Hypervariability
Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (
Disulfide connectivities
Types of conotoxins also differ in the number and pattern of disulfide bonds.[9] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.[10]
Types and biological activities
The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. Each of the five types of conotoxins attacks a different target:
- α-conotoxin inhibits nicotinic acetylcholine receptors at nerves and muscles.[11]
- δ-conotoxin inhibits fast inactivation of voltage-dependent sodium channels.[12]
- κ-conotoxin inhibits potassium channels.[13]
- μ-conotoxin inhibits voltage-dependent sodium channels in muscles.[14]
- ω-conotoxin inhibits N-type
Alpha
Alpha conotoxins have two types of cysteine arrangements,[18] and are competitive nicotinic acetylcholine receptor antagonists.
Delta, kappa, and omega
Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine knot scaffold. The knottin scaffold is a very special disulfide-through-disulfide knot, in which the III-VI disulfide bond crosses the macrocycle formed by two other disulfide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N-terminus. The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers.[9]
Mu
Mu-conotoxin | |||||||||
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OPM superfamily | 112 | ||||||||
OPM protein | 1ag7 | ||||||||
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Mu-conotoxins have two types of cysteine arrangements, but the
Different subtypes of voltage-gated sodium channels are found in different tissues in mammals, e.g., in muscle and brain, and studies have been carried out to determine the sensitivity and specificity of the mu-conotoxins for the different isoforms.[23]
See also
- Conolidine
- Contryphan, members of "conotoxin O2"
- Conantokins, also known as "conotoxin B"
References
- PMID 14715910.
- PMID 17932414.
- ^ "Archived copy" (PDF). Archived (PDF) from the original on 2017-08-29. Retrieved 2017-03-31.
{{cite web}}
: CS1 maint: archived copy as title (link) - ^ "Biological Agent Reference Sheet - Conotoxin" (PDF). Emory University.
- ^ Baker, A.L. "toxin ld50 list". PhycoKey.
- PMID 22954218.
- PMID 22285376.
- PMID 21511358.
- ^ PMID 11478951.
- PMID 10988292.
- PMID 15182346.
- PMID 15990094.
- PMID 9417043.
- PMID 15246758.
- PMID 10822250. Archived from the original(abstract) on 2011-08-13.
- PMID 9792182.
- PMID 16845440.
- PMID 1390774.
- ^ PMID 12006587.
- PMID 2410412.
- PMID 11478951.
- PMID 2410412.
- PMID 12878039.
External links
- Conotoxins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Baldomero "Toto" Olivera's Short Talk. "Conus Peptides".
- Kaas Q, Westermann JC, Halai R, Wang CK, Craik DJ. "ConoServer". Institute of Molecular Bioscience, The University of Queensland, Australia. Retrieved 2009-06-02.
A database for conopeptide sequences and structures