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Family: Myotoxins (PF00819)

Summary: Myotoxin, crotamine

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This is the Wikipedia entry entitled "Crotamine". More...

Crotamine Edit Wikipedia article

The protein structure of crotamine (PDB:1H5O)

Crotamine is a toxin present in the venom of the South American rattlesnake (Crotalus durissus terrificus). It is a 42-residue long protein containing 11 basic residues (9 lysines, 2 arginines) and 6 cysteines. It has also been isolated from the venom of North American prairie rattlesnake, Crotalus viridis viridis. It was first isolated and purified by Brazilian scientist José Moura Gonçalves, and later intensively studied by his group of collaborators at the Medical School of Ribeirão Preto of the University of São Paulo.

Biological function

Crotamine has a number of biological actions: it acts on cell membrane's sodium channels, is slightly analgesic and is myotoxic, i.e., it penetrates the cells of muscles and promotes necrosis. Crotamine is homologous with other venom myotoxins and is similar to α-,β-defensins.

Biochemistry and mechanism

The amino acid sequence, YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGS—G, and the 3D molecular structure of crotamine have already been determined.

The protein structure of crotamine could not be initially determined through protein crystallization nor X-ray diffraction.[1] It was speculated that the difficulty was because crotamine has so many isoforms, leading to the formation of aggregates and different possible conformations of the protein. The structure and the shape of the protein was proposed through a 3D model generated by Siqueira et al. (2002) based on computational calculations that were supported with intensive molecular dynamics simulations and homology modeling procedures. Afterwards, Nicastro et al. (2003) discovered the structure of crotamine through nuclear magnetic resonance spectroscopy. Crotamine has a topology that was never before seen in active toxins that target ion channels; the protein is composed of a short N-terminal alpha helix, a type of protein formation, and a small antiparallel triple-stranded beta-sheet, another type of protein formation, arranged in an ab1b2b3 topology. Crotamine has similar structural fold conformations to the human b-defensin family as well as identical disulfide bridges arrangement.[2]

[Figure needed]

The gene and chromosome location responsible for its synthesis have been identified by the group led by Gandhi Rádis-Baptista, working at the Instituto Butantan, in São Paulo, Brazil. The mRNA has about 340 nucleotides and codifies a pre-crotamine, including the signal peptide, the mature crotamine, and a final lysine.

The Crotamine gene was the first gene to be mapped on a snake chromosome.[3] The gene responsible for coding the crotamine protein is labeled as Crt-p1 and its base pair sequence length is about 1.1kbp or 1100 bp. It was reported that the crotamine gene was isolated twice from two different specimens, one in a method that resulted in a gene size of 1.8 kbp and in the other specimen a gene size of 1.1 kbp.[4] The gene has been previously isolated in the C. durissus terrificus genome and the protein itself belongs to a group of small basic polypeptide myotoxins (SBPM). The contents of Crotalus venoms can vary according to subspecies and geographical location.[5] The Crt-p1 gene, as described by Radis-Bastista et al. 2003, consists of about three exons separated by one short phase-2 (140 bp) and one long phase-1 (900 bp) intron. Exon 1 codes for the first 19 amino acids of the signal peptide and includes the 5’-untranslated region. Exon 2 codes 39 amino acids to the mature crotamine and three signal peptide amino acids. Exon 3 codes for the terminal lysine and the last three amino acids of the mature toxin. Research on SBPM amino acid sequences among different Crotalus species has revealed a high degree of likeness ranging from 83% - 98%.[6][7]

The amino acid code of proteins in the small basic polypeptide myotoxin family, which includes crotamine, have been sequenced. They were found to be similar with an average of 83% divergence. A crotamine amino acid sequence was compared to that of cloned DNA of myotoxin a, (the myotoxin used to model how SBPMs work). In the comparison, exon coding regions including the mature myotoxin and the signal peptide were 98% and 100% similar, respectively. The untranslated regions for 5’ and 3’ between the sample and the myotoxin a cDNA was 60% and 80%, respectively. When comparing the amino acid sequences of other proteins not in the SBPM family found in snake venoms, there is usually large divergence. When looking at the SBPM proteins, they have high similarity between different subspecies of the Crotalus genus and between different individuals of the same subspecies. This indicates, according to the Radis-Batista et al. 2003 study, that the crotamine gene and other SBPM genes have evolved recently.

References

  1. ^ Boni-Mitake, M., Ra´dis-Baptistam , G., Oguiura, N., 2005. New view on crotamine, a small basic polypeptide myotoxin from South American rattlesnake venom. Toxicon 46, 363-370. < http://www.ipen.br/biblioteca/2005/11186.pdf>
  2. ^ Boni-Mitake, M., Ra´dis-Baptistam , G., Oguiura, N., 2005. New view on crotamine, a small basic polypeptide myotoxin from South American rattlesnake venom. Toxicon 46, 363-370. < http://www.ipen.br/biblioteca/2005/11186.pdf>
  3. ^ Boni-Mitake, M., Ra´dis-Baptistam , G., Oguiura, N., 2005. New view on crotamine, a small basic polypeptide myotoxin from South American rattlesnake venom. Toxicon 46, 363-370. < http://www.ipen.br/biblioteca/2005/11186.pdf>.
  4. ^ Samejima, Y., Aoki, Y., Mebs, D., 1991. Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake(Crotalus adamanteus). Toxicon 29, 461–468.
  5. ^ Schenberg, S., 1959. Geographical pattern of crotamine distribution in the same rattlesnake subspecies. Science 129, 1361–1363.
  6. ^ Samejima, Y., Aoki, Y., Mebs, D., 1991. Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake(Crotalus adamanteus). Toxicon 29, 461–468.
  7. ^ Ownby, C., 1998. Structure, function and biophysical aspects of the myotoxins from snake venoms. J. Toxicol. Toxin. Rev. 17, 213–238.

Further reading

  • Siqueira, A.M., Martins, N.F., Lima, M.E. de, Diniz, C.R., Cartier, A., Brown, D., Maigret, B., 2002. A proposed 3D structure for crotamine based on homology building, molecular simulations and circular ichroism. J. Mol. Graph. Model. 20, 389–398.
  • Gonçalves JM, Deutsch HF. Ultracentrifugal and zone electrophoresis studies of some crotalidae venoms. Arch Biochem Biophys. 1956 Feb;60(2):402-11. doi:10.1016/0003-9861(56)90444-1 PMID 13292919
  • Giglio JR. Analytical studies on crotamine hydrochloride. Anal Biochem. 1975 Nov;69(1):207-21. PMID 2030
  • Laure CJ. The primary structure of crotamine. Hoppe Seylers Z Physiol Chem. 1975 Feb;356(2):213-5. German. PMID 1176086
  • De Lucca FL, Imaizumi MT, Haddad A. Characterization of ribonucleic acids from the venom glands of Crotalus durissus terrifucus (Ophidia, Reptilia) after manual extraction of the venom. Studies on template activity and base composition. Biochem J. 1974 Apr;139(1):151-6. PMID 4463939
  • Ownby, C. L., Cameron, M. S., and Tu, A. T. (1976) Isolation of myotoxin component from rattlesnake (Crotalus viridis viridis) venom. Am. J. Pathol. 85, 149–166
  • Rádis-Baptista, G., Oguiura, N., Hayashi, M. A. F., Camargo, M. E., Grego, K. F., Oliveira, E. B., and Yamane, T. (1999) Nucleotide sequence of crotamine isoform precursors from a single South American rattlesnake (Crotalus durissus terrificus). Toxicon 37, 973–984
  • Alexandre Kerkis, Irina Kerkis, Gandhi Rádis-Baptista, Eduardo B. Oliveira, Angela M. Vianna-Morgante, Lygia V. Pereira, and Tetsuo Yamane. Crotamine is a novel cell-penetrating protein from the venom of rattlesnake Crotalus durissus terrificus. The FASEB Journal Express Article doi:10.1096/fj.03-1459fje. Published online July 1, 2004
  • Radis-Baptista G, Kubo T, Oguiura N, Prieto da Silva AR, Hayashi MA, Oliveira EB, Yamane T. Identification of crotasin, a crotamine-related gene of Crotalus durissus terrificus. Toxicon. 2004 Jun 1;43(7):751-9. PMID 15284009
  • Radis-Baptista G, Kubo T, Oguiura N, Svartman M, Almeida TM, Batistic RF, Oliveira EB, Vianna-Morgante AM, Yamane T. Structure and chromosomal localization of the gene for crotamine, a toxin from the South American rattlesnake, Crotalus durissus terrificus. Toxicon. 2003 Dec;42(7):747-52. PMID 14757205
  • Nicastro G, Franzoni L, de Chiara C, Mancin AC, Giglio JR, Spisni A. Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom. Eur J Biochem. 2003 May;270(9):1969-79. PMID 12709056
  • Mouhat S, Jouirou B, Mosbah A, De Waard M, Sabatier JM. Diversity of folds in animal toxins acting on ion channels. Biochem J. 2004 Mar 15;378(Pt 3):717-26. PMID 14674883

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Myotoxin". More...

Myotoxin Edit Wikipedia article

Myotoxin
Crotamin 1H5O.png
Structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom.[1]
Identifiers
Symbol Myotoxins
Pfam PF00819
InterPro IPR000881
PROSITE PDOC00435
SCOP 1h5o
SUPERFAMILY 1h5o

Myotoxins are small, basic peptides found in snake venoms, (e.g. rattlesnakes),[2][3] and lizard venoms (e.g. mexican beaded lizard).[4] This involves a non-enzymatic mechanism that leads to severe muscle necrosis. These peptides act very quickly, causing instantaneous paralysis to prevent prey from escaping and eventually death due to diaphragmactic paralysis.

The first myotoxin to be identified and isolated was crotamine, from the venom of Crotalus durissus terrificus, a tropical South American rattlesnake, by Brazilian scientist José Moura Gonçalves, in the 1950s. Its biological actions, molecular structure and gene responsible for its synthesis were all elucidated in the last two decades.

References

  1. ^ Nicastro G, Franzoni L, de Chiara C, Mancin AC, Giglio JR, Spisni A (May 2003). "Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom". Eur. J. Biochem. 270 (9): 1969–79. doi:10.1046/j.1432-1033.2003.03563.x. PMID 12709056. 
  2. ^ Griffin PR, Aird SD (1990). "A new small myotoxin from the venom of the prairie rattlesnake (Crotalus viridis viridis)". FEBS Lett. 274 (1): 43–47. doi:10.1016/0014-5793(90)81325-I. PMID 2253781. 
  3. ^ Samejima Y, Aoki Y, Mebs D (1991). "Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake (Crotalus adamanteus)". Toxicon. 29 (4): 461–468. doi:10.1016/0041-0101(91)90020-r. PMID 1862521. 
  4. ^ Whittington, CM; Papenfuss, AT; Bansal, P; Torres, AM; Wong, ES; Deakin, JE; Graves, T; Alsop, A; Schatzkamer, K; Kremitzki, C; Ponting, CP; Temple-Smith, P; Warren, WC; Kuchel, PW; Belov, K (Jun 2008). "Defensins and the convergent evolution of platypus and reptile venom genes.". Genome Research. 18 (6): 986–94. doi:10.1101/gr.7149808. PMC 2413166Freely accessible. PMID 18463304. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Myotoxin, crotamine Provide feedback

Crotamine is a family of cationic peptides expressed by the venom gland of, for example, Crotalus durissus terrificus. It acts as a cell-penetrating peptide (CPP) and as a potent voltage-gated potassium channel (Kv) inhibitor [1-6].

Literature references

  1. Nicastro G, Franzoni L, de Chiara C, Mancin AC, Giglio JR, Spisni A;, Eur J Biochem. 2003;270:1969-1979.: Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom. PUBMED:12709056 EPMC:12709056

  2. Fadel V, Bettendorff P, Herrmann T, de Azevedo WF Jr, Oliveira EB, Yamane T, Wuthrich K;, Toxicon. 2005;46:759-767.: Automated NMR structure determination and disulfide bond identification of the myotoxin crotamine from Crotalus durissus terrificus. PUBMED:16185738 EPMC:16185738

  3. Radis-Baptista G, Kubo T, Oguiura N, Prieto da Silva AR, Hayashi MA, Oliveira EB, Yamane T;, Toxicon. 2004;43:751-759.: Identification of crotasin, a crotamine-related gene of Crotalus durissus terrificus. PUBMED:15284009 EPMC:15284009

  4. Kerkis A, Kerkis I, Radis-Baptista G, Oliveira EB, Vianna-Morgante AM, Pereira LV, Yamane T;, FASEB J. 2004;18:1407-1409.: Crotamine is a novel cell-penetrating protein from the venom of rattlesnake Crotalus durissus terrificus. PUBMED:15231729 EPMC:15231729

  5. Yount NY, Kupferwasser D, Spisni A, Dutz SM, Ramjan ZH, Sharma S, Waring AJ, Yeaman MR;, Proc Natl Acad Sci U S A. 2009;106:14972-14977.: Selective reciprocity in antimicrobial activity versus cytotoxicity of hBD-2 and crotamine. PUBMED:19706485 EPMC:19706485

  6. Peigneur S, Orts DJ, Prieto da Silva AR, Oguiura N, Boni-Mitake M, de Oliveira EB, Zaharenko AJ, de Freitas JC, Tytgat J;, Mol Pharmacol. 2012;82:90-96.: Crotamine pharmacology revisited: novel insights based on the inhibition of KV channels. PUBMED:22498659 EPMC:22498659


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000881

Myotoxins are small basic peptides (42 to 45 residues) that can cause severe muscle necrosis by a non-enzymatic mechanism. They act extremely rapidly and serve two primary biological functions: limiting the flight of prey by causing instantaneous paralysis of the hind limbs and promoting rapid death by paralysis of the diaphragm [PUBMED:2253781, PUBMED:1862521]. These myotoxins have a well-conserved structure containing six cysteines involved in three disulphide bridges.

One of the better studied myotoxins is crotamine, from South American rattlesnake Crotalus durissus terrificus. Crotamine is a multifunctional peptide with pharmacological interest; it can penetrate cells and has potential selective antitumoral activity together with its ability to inhibit the potassium current through voltage-gated potassium channels [PUBMED:22498659]. Similar toxins have been isolated from the venom of other rattlesnake species [PUBMED:16115660].

Gene Ontology

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Pfam Clan

This family is a member of clan Defensin (CL0075), which has the following description:

This clan includes diverse defensins as well as myotoxins.

The clan contains the following 10 members:

Defensin_1 Defensin_3 Defensin_4 Defensin_beta Defensin_beta_2 Defensin_big Inhibitor_I68 Meleagrin Myotoxins Toxin_4

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Seed source: Pfam-B_1337 (release 2.1)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 2
Number in full: 0
Average length of the domain: 0.00 aa
Average identity of full alignment: 0 %
Average coverage of the sequence by the domain: 0.00 %

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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 80.4 80.3
Noise cut-off 23.4 22.9
Model length: 43
Family (HMM) version: 16
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