Conus Peptides and Biotechnology

Olivera, Baldomero M.; Cruz, Lourdes J.; Myers, Richard A.; Hillyard, David R.; Rivier, Jean; Scott, Jamie K.

doi:10.1007/978-94-011-2898-8_4

Cited by 28 publications

(46 citation statements)

References 14 publications

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“…1). Twenty-one of the final forty-seven residues in Agouti protein and Agrp are identical, of which ten residues are cysteines in a spacing similar to that found in conotoxins and plectoxins from the venoms of cone snails (34) and spiders (35), respectively. In addition, the amino terminus of the Agouti protein contains several paired basic residues that could serve as potential proteolytic cleavage sites (Fig.…”

Section: Agouti Protein Is Present In Mouse Skin In the Full-lengthmentioning

confidence: 92%

“…Calcium channels are the direct targets for most of the -conotoxins (reviewed in Ref. 34), but the same is unlikely to be true for Agouti protein because it binds the Mc1r and its pigmentary effects are completely blocked by deficiency for the Mc1r (25). Nonetheless, an ancestral pattern of protein folding common to the endogenous melanocortin receptor antagonists and invertebrate toxins may serve as a scaffold for interaction with a diverse group of cell surface proteins, and binding of the Mc1r by Agouti protein may lead indirectly to changes in calcium metabolism that have been reported in certain cell culture systems.…”

Section: A Unique Role For the Amino Terminus Of Agouti Proteinunlikementioning

confidence: 99%

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Down-regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in XenopusMelanophores

Ollmann¹,

Barsh

1999

Journal of Biological Chemistry

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To investigate the potential role of the amino-terminal residues, we compared the function of full-length and carboxyl-terminal fragments of Agrp and Agouti protein in a sensitive bioassay based on pigment dispersion in Xenopus melanophores. We find that carboxyl-terminal Agouti protein, and all forms of Agrp tested, act solely by competitive antagonism of melanocortin action. However, full-length Agouti protein acts by an additional mechanism that is time-and temperature-dependent, depresses maximal levels of pigment dispersion, and is therefore likely to be mediated by receptor down-regulation. Apparent down-regulation is not observed for a mixture of amino-terminal and carboxyl-terminal fragments. We propose that the phenotypic effects of Agouti in vivo represent a bipartite mechanism: competitive antagonism of agonist binding by the carboxyl-terminal portion of Agouti protein and down-regulation of melanocortin receptor signaling by an unknown mechanism that requires residues in the amino terminus of the Agouti protein.

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Section: Agouti Protein Is Present In Mouse Skin In the Full-lengthmentioning

confidence: 92%

Section: A Unique Role For the Amino Terminus Of Agouti Proteinunlikementioning

confidence: 99%

Down-regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in XenopusMelanophores

Ollmann¹,

Barsh

1999

Journal of Biological Chemistry

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“…Venom is injected to stun prey and contains a wide variety of neurotoxins (''conotoxins'') that block a diversity of ion channels and neuronal receptors (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) in prey species. Different conotoxins are maximally effective on different prey species (6)(7)(8)(17)(18); the ability to prey on these taxa among Conus species is thus linked to conotoxin evolution. To illuminate the genetic basis of ecological diversification in cone snails, we have begun to investigate the molecular evolution of conotoxins.…”

mentioning

confidence: 99%

Molecular genetics of ecological diversification: Duplication and rapid evolution of toxin genes of the venomous gastropod Conus

Duda

Palumbi

1999

Proc. Natl. Acad. Sci. U.S.A.

307

245

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Predatory snails in the marine gastropod genus Conus stun prey by injecting a complex mixture of peptide neurotoxins. These conotoxins are associated with trophic diversification and block a diverse array of ion channels and neuronal receptors in prey species, but the evolutionary genesis of this functional diversity is unknown. Here we show that conotoxins with little amino acid similarity are in fact products of recently diverged loci that are rapidly evolving by strong positive selection in the vermivorous cone, Conus abbreviatus, and that the rate of conotoxin evolution is higher than that of most other known proteins. Gene duplication and diversifying selection result in the formation of functionally variable conotoxins that are linked to ecological diversification and evolutionary success of this genus.

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“…Most conotoxins are small, highly constrained and specialized polypeptides present in the venom produced by marine cone snails (Conus) (13). A distinctive characteristic of the conotoxins is the high percentage of cysteine residues mediating disulfide bridges in many of the peptides.…”

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confidence: 99%

A Novel Post-translational Modification Involving Bromination of Tryptophan

Craig

Jimenéz

Dykert

et al. 1997

Journal of Biological Chemistry

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100

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We report a novel post-translational modification involving halogenation of tryptophan in peptides recovered from the venom of carnivorous marine cone snails (Conus). The residue, L-6-bromotryptophan, was identified in the sequence of a heptapeptide, isolated from Conus imperialis, a worm-hunting cone. This peptide does not elicit gross behavioral symptoms when injected centrally or peripherally in mice. L-6-Bromotryptophan was also identified in a 33-amino acid peptide from Conus radiatus; this peptide has been shown to induce a sleep-like state in mice of all ages and is referred to as bromosleeper peptide. The sequences of the two peptides Pca-Cys-Gly-Gln-Ala-Trp*-Cys-NH 2 were determined using a combination of mass spectrometry, amino acid, and chemical sequence analyses, where Pca ‫؍‬ pyroglutamic acid, Hyp ‫؍‬ hydroxyproline, Gla ‫؍‬ ␥-carboxyglutamate, and Trp* ‫؍‬ L-6-bromotryptophan. The precise structure and stereochemistry of the modified residue were determined as L-6-bromotryptophan by synthesis, co-elution, and enzymatic hydrolysis experiments. To our knowledge this is the first documentation of tryptophan residues in peptides/proteins being modified in a eukaryotic system and the first report of halogenation of tryptophan in vivo. SEQUENCE 1 andPolypeptides encoded by genes are primarily made up of the 20 common amino acids that are directly translated using the genetic code. However, many of these amino acids can be further modified post-translationally to yield a set of additional amino acids that contribute to the function of the mature protein. Together the 20 primary amino acids and these "secondary" amino acids which are found in proteins comprise the set of proteinogenous amino acids.These modified amino acids include amino acid conjugates where the side chain is linked to a glycosyl, phosphate, or sulfate group and amino acids such as 5-hydroxylysine, 4-hydroxyproline, and ␥-carboxyglutamate. One notable set of modified amino acids are halogenated derivatives of tyrosine and histidine. Naturally occurring halogenated tyrosine and histidine residues have previously been identified from proteins (1-4). A particularly well documented example of in vivo posttranslational halogenation of an amino acid residue in a protein is afforded by thyroglobulin (5). After iodination of several tyrosine residues, selective cleavages release the iodinated thyroid hormones thyroxine (3,5,3Ј,5Ј-tetraiodothyronine or T 4 ) 1 ; 3,5,3Ј-triiodothyronine (T 3 ), and 3,3Ј-di-iodothyronine. The presence of free T 3 and T 4 has also been shown in protochordates, suggesting a primitive thyroid function exists in tunicates (2).Of the 20 common amino acids, alanine, glycine, isoleucine, leucine, and valine, which lack side chain functional groups, have not been implicated in post-translational modifications (6). In 1907 it was proposed that hydroxytryptophan was a proteinogenous amino acid (7), but this proposal has not been verified (1), and chemical oxidation of tryptophan is likely to be responsible for the observed ...

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Conus Peptides and Biotechnology

Cited by 28 publications

References 14 publications

Down-regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in XenopusMelanophores

Down-regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in XenopusMelanophores

Molecular genetics of ecological diversification: Duplication and rapid evolution of toxin genes of the venomous gastropod Conus

A Novel Post-translational Modification Involving Bromination of Tryptophan

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