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'''Calitoxin''', also known as '''CLX''', is a ] |
'''Calitoxin''', also known as '''CLX''', is a ] produced by the sea anemone ''Calliactis parasitica''. Two isoforms (CLX-1 and CLX-2) have been identified, both of which are formed from precursors stored in the ]s of the anemone. It targets crabs and octopuses, among other invertebrates. Once the toxin is activated and released, it causes paralysis by increasing ] at invertebrate neuromuscular junctions. Along with several other toxins derived from anemones, it is useful in ] research<ref name="car">{{cite journal|last1=Cariello|first1=L|last2=de Santis|first2=A|last3=Fiore|first3=F|last4=Piccoli|first4=R|last5=Spagnuolo|first5=A|last6=Zanetti|first6=L|last7=Parente|first7=A|title=Calitoxin, a neurotoxic peptide from the sea anemone Calliactis parasitica: amino acid sequence and electrophysiological properties.|journal=Biochemistry|date= 21 Mar 1989|volume=28|issue=6|pages=2484–9|pmid=2567180|accessdate=13 October 2014}}</ref> <ref name="spag">{{cite journal|last1=Spagnuolo|first1=Antonietta|last2=Zanetti|first2=Laura|last3=Cariello|first3=Lucio|last4=Piccoli|first4=Renata|title=Isolation and characterization of two genes encoding calitoxins, neurotoxic peptides from Calliactis parasitica (Cnidaria)|journal=Gene|volume=138|issue=1-2|pages=187–191|doi=10.1016/0378-1119(94)90805-2}}</ref> | ||
== Discovery == | == Discovery == | ||
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== Structure and chemistry == | == Structure and chemistry == | ||
The formula for calitoxin is C<sub>203</sub>H<sub>305</sub>N<sub>55</sub>O<sub>72</sub>S<sub>7</sub>. It has a molecular mass of mass of 4886 ]s. It has an ] at pH 5.4.<ref name="spag" /> The ] is markedly dissimilar from other known sea anemones toxins. There are two known genes coding for two highly ] calitoxins. They are CLX-1 and CLX-2, both consisting of 46 amino acids with three ]s.<ref name=Kastin /> Both originate from a |
The formula for calitoxin is C<sub>203</sub>H<sub>305</sub>N<sub>55</sub>O<sub>72</sub>S<sub>7</sub>. It has a molecular mass of mass of 4886 ]s. It has an ] at pH 5.4.<ref name="spag" /> The ] is markedly dissimilar from other known sea anemones toxins. There are two known genes coding for two highly ] calitoxins. They are CLX-1 and CLX-2, both consisting of 46 amino acids with three ]s.<ref name=Kastin /> Both originate from a precursor peptide of 79 amino acids where the ] determines whether it will be the mature CLX-1 or CLX-2. Researchers consider that these precursors may be stored in ]. Under the effects of some triggering stimulus, the precursor would be modified and released in the active form. The patterning of cleavage sites targeted during maturation of the peptide suggest that the active ] might be a tetrapeptide.<ref name="RappuoliMontecucco1997" /> | ||
{| class="wikitable" | {| class="wikitable" | ||
!style="background-color:#FFDEAD;"|Isoform | !style="background-color:#FFDEAD;"|Isoform |
Revision as of 15:30, 19 November 2014
Identifiers | |
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CAS Number | |
Abbreviations | CLX |
CompTox Dashboard (EPA) | |
Properties | |
Chemical formula | C203H305N55O72S7 |
Molar mass | 4892.41 g·mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references |
Calitoxin | |||||||
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Identifiers | |||||||
Organism | Calliactis parasitica | ||||||
Symbol | CLX | ||||||
UniProt | P14531 | ||||||
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Identifiers | |||||||||
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Symbol | ? | ||||||||
Pfam | PF00706 | ||||||||
InterPro | IPR000693 | ||||||||
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Calitoxin, also known as CLX, is a sea anemone neurotoxin produced by the sea anemone Calliactis parasitica. Two isoforms (CLX-1 and CLX-2) have been identified, both of which are formed from precursors stored in the stinging cells of the anemone. It targets crabs and octopuses, among other invertebrates. Once the toxin is activated and released, it causes paralysis by increasing neurotransmitter release at invertebrate neuromuscular junctions. Along with several other toxins derived from anemones, it is useful in ion channel research
Discovery
The name calitoxin derives from the organism the toxin was isolated from – the sea anemone Calliactis parasitica. The toxin was isolated by a team of researchers in Naples, Italy from animals collected from the Bay of Naples. The team isolated the polypeptide through a series of centrifugations until the supernatant had lost toxic activity. The resulting pellet was purified using techniques of liquid chromatography, gel filtration, and chromatofocusing. The team then sequenced the purified polypeptide chain. They also published details on the toxins effects in vitro on crustacean tissue preparations, including nerve and muscle. Their findings were published in the journal Biochemistry in 1989.
Sources
Calitoxin is a highly potent neurotoxin produced by the sea anemone Calliactis parasitica, then stored in the nematocysts of stinging cells (cnidocytes). This sea anemone is a species from the Hormathiidae family and is present along the European coasts of the Atlantic Ocean and in the Mediterranean Sea.
Structure and chemistry
The formula for calitoxin is C203H305N55O72S7. It has a molecular mass of mass of 4886 Daltons. It has an isoelectric point at pH 5.4. The amino acid sequence is markedly dissimilar from other known sea anemones toxins. There are two known genes coding for two highly homologous calitoxins. They are CLX-1 and CLX-2, both consisting of 46 amino acids with three disulfide bonds. Both originate from a precursor peptide of 79 amino acids where the C-terminus determines whether it will be the mature CLX-1 or CLX-2. Researchers consider that these precursors may be stored in cnidocytes. Under the effects of some triggering stimulus, the precursor would be modified and released in the active form. The patterning of cleavage sites targeted during maturation of the peptide suggest that the active quaternary structure might be a tetrapeptide.
Isoform | Sequence | Location disulfide bridges |
---|---|---|
CLX-1 precursor | MKTQVLALFV LCVLFCLAES RTTLNKRNDI EKRIECKCEG DAPDLSHMTG TVYFSCKGGD GSWSKCNTYT AVADCCHQA | 36–75, 38-66, 56–76 |
CLX-2 precursor | MKTQVLAVFV LCVLFCLAES RTTLNKRIDI AKRIECKCKG DAPDLSHMTG TVYFSCKGGD GSWSKCNTYT AVADCCHQA | 36–75, 38-66, 56–76 |
Calitoxin and other sea anemome toxins are used in studying ion channels, with potential applications in biomedical and physiology research.. In the mature CLX, one base-pair substitution is responsible for a single glutamic acid to lysine replacement in the coding region of CLX-2, leading to the difference between the two peptides. The structural organization of these two genes show a high degree of homology. This might imply that the two different peptides have the same biological function. This cannot yet be confirmed because only CLX-1 has been isolated from C. parasitica. Calitoxin has a low degree of homology another sodium channel binding sea anemone toxin, ATX II, which might offer insights in the function of particular amino acid residues. Despite markedly dissimilar gene sequences, CLX-1 affects crustacean axon potentials similar to two other known classes of sea anemone toxins. Certain aspects of the structure of the CLX genes are found in scorpion toxins as well as other sea anemone toxins that block potassium channels.
Target and mode of action
Calitoxin causes massive neurotransmitter release from the nerve terminals of the neuromuscular junction, which in turn causes a strong muscle contraction and even paralysis. The exact target of calitoxin has not yet been clarified; because it has a similar action on the neuromuscular junction as Anemonia sulcata toxins, Calitoxin has been proposed to slow down the inactivation of voltage-gated sodium channels in motor neurons.
Function in nature
Sea anemones produce toxins, such as calitoxin, in their stinging cells (cnidocytes). These cells contain organelles called nematocysts. When triggered, an envenomation response occurs. This can result in injury to target organisms, including capture of prey, defense against predatory organisms, or against aggressors from within their own species. In a natural setting, C. parasitica establishes a mutualistic relationship with the hermit crab Pagurus bernhardus. The sea anemone identifies shells inhabited by the hermit crab and attaches. Through stings against potential predators, C. parasitica provides protection for the hermit crab. In return, the sea anemone gains an advantage in accessing a broader distribution of food sources, as the crab moves across the ocean floor. Octopuses will avoid shells bearing C. parasitica.
Toxicity
Calitoxin has been tested for activity on the crab Carcinus mediterraneus. Purified toxin was injected into the hemocoel of the crab. The minimum dose of 0.2 µg of toxin triggered muscle contractions in the crab, causing paralysis within 1 minute. The LD50 is unknown.
References
- ^ Cariello, L; de Santis, A; Fiore, F; Piccoli, R; Spagnuolo, A; Zanetti, L; Parente, A (21 Mar 1989). "Calitoxin, a neurotoxic peptide from the sea anemone Calliactis parasitica: amino acid sequence and electrophysiological properties". Biochemistry. 28 (6): 2484–9. PMID 2567180.
{{cite journal}}
:|access-date=
requires|url=
(help) - ^ Spagnuolo, Antonietta; Zanetti, Laura; Cariello, Lucio; Piccoli, Renata. "Isolation and characterization of two genes encoding calitoxins, neurotoxic peptides from Calliactis parasitica (Cnidaria)". Gene. 138 (1–2): 187–191. doi:10.1016/0378-1119(94)90805-2.
- ^ Rappuoli, Rino; Montecucco, Cesare (29 May 1997). Guidebook to Protein Toxins and Their Use in Cell Biology. Oxford University Press, UK. pp. 139–. ISBN 978-0-19-154728-7. Retrieved 18 November 2014.
- ^ Kastin, edited by Abba J. (2006). Handbook of biologically active peptides. Amsterdam: Academic Press. pp. 363–364. ISBN 0-12-369442-6.
{{cite book}}
:|first1=
has generic name (help) - "Calitoxin-1". UniProt.
- "Calitoxin-2". UniProt.
- Nagai, Hiroshi (2012). "Special Issue "Sea Anemone Toxins"". Marine Drugs. Retrieved 19 November 2014.
- Q. Ashton Acton, PhD. "Neurologic Manifestations—Advances in Research and Treatment: 2013 Edition". ScholarlyEditions, 2013. p. 60. Retrieved 18 November 2014.
- Moran, Yehu; Gordon, Dalia; Gurevitz, Michael (December 2009). "Sea anemone toxins affecting voltage-gated sodium channels – molecular and evolutionary features". Toxicon. 54 (8): 1089–1101. doi:10.1016/j.toxicon.2009.02.028.
{{cite journal}}
:|access-date=
requires|url=
(help) - John Fish & Susan Fish (2011). "Calliactis parasitica (Couch)". A Student's Guide to the Seashore (3rd ed.). Cambridge University Press. p. 96. ISBN 978-0-521-72059-5.
- Roger T. Hanlon & John B. Messenger (1998). "Learning and the development of behaviour". Cephalopod Behaviour. Cambridge University Press. pp. 132–148. ISBN 978-0-521-64583-6.