A novel 13 residue acyclic peptide from the marine snail, Conus monile, targets potassium channels

Sudarslal, S; Singaravadivelan, G.; Ramasamy, P.; Ananda, K.; Sarma, Siddhartha P.; Sikdar, Siddhartha; Krishnan, K. S.; Balaram, Padmanabhan

doi:10.1016/j.bbrc.2004.03.100

Cited by 30 publications

(23 citation statements)

References 25 publications

(22 reference statements)

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“…6 and Table 1 could be obtained. A small peptide lacking disulfides that inhibited voltage-gated K ϩ channels was reported previously from Conus monile; the subfamily selectivity was not reported (20). The CPY peptide that has been most well characterized, CPY-Pl1, is highly selective for the Kv1.6 subtype.…”

Section: Discussionmentioning

confidence: 95%

Tyrosine-rich Conopeptides Affect Voltage-gated K+ Channels

Imperial

Chen

Sporning

et al. 2008

Journal of Biological Chemistry

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Two venom peptides, CPY-Pl1 (EU000528) and CPY-Fe1 (EU000529), characterized from the vermivorous marine snails Conus planorbis and Conus ferrugineus, define a new class of conopeptides, the conopeptide Y (CPY) family. The peptides have no disulfide cross-links and are 30 amino acids long; the high content of tyrosine is unprecedented for any native gene product. The CPY peptides were chemically synthesized and shown to be biologically active upon injection into both mice and Caenorhabditis elegans; activity on mammalian Kv1 channel isoforms was demonstrated using an oocyte heterologous expression system, and selectivity for Kv1.6 was found. NMR spectroscopy revealed that the peptides were unstructured in aqueous solution; however, a helical region including residues 12-18 for one peptide, CPY-Pl1, formed in trifluoroethanol buffer. Clones obtained from cDNA of both species encoded prepropeptide precursors that shared a unique signal sequence, indicating that these peptides are encoded by a novel gene family. This is the first report of tyrosine-rich bioactive peptides in Conus venom.The venom of marine gastropods in the genus Conus has yielded numerous structurally and functionally diverse peptidic components (1). The increasing variety of bioactive peptides identified in cone snail venoms has provided insight into the seemingly endless variety of directions taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes.The bioactive peptides in Conus ("conopeptides") are classified into two broad groups: the non-disulfide-rich and the disulfide-rich (1). The latter are conventionally called conotoxins. The non-disulfide-rich class includes conopeptides with no cysteines (contulakins (2), conantokins (3), and conorfamides (4)) and conopeptides with two cysteines forming a single disulfide bond (conopressins (5) and contryphans (6)). The conopeptides that compose the disulfide-rich class have two or more disulfide bonds (1); among the major classes of molecular targets identified for these structurally diverse conopeptides are members of the voltage-gated and ligand-gated ion channel superfamilies.In this work, we present the discovery and characterization of a novel class of peptides, which we designate the conopeptide Y (CPY) 2 family, from the marine snails Conus planorbis and Conus ferrugineus (see Fig. 1). Both of these species belong to a distinct clade of Conus (7, 8). The first two peptides (9) belonging to the CPY family have a high frequency of tyrosine residues, in addition to basic and hydrophobic residues. The peptides are shown to be biologically active when injected into mouse and the nematode Caenorhabditis elegans. Activity on the Kv1 channel subfamily is demonstrated, and the subtype selectively within the subfamily is defined. EXPERIMENTAL PROCEDURES Extraction and Fractionation of C. planorbis Venom-Snailswere collected in Cebu and Marinduque Islands, Philippines, and dissected. Venom was pressed out of freshly dissected venom ducts that were kept on ice. V...

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Section: Discussionmentioning

confidence: 95%

Tyrosine-rich Conopeptides Affect Voltage-gated K+ Channels

Imperial

Chen

Sporning

et al. 2008

Journal of Biological Chemistry

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“…e novo sequencing by mass spectrometry is rapidly emerging as the method of choice for the characterization of the peptides from natural sources [1][2][3][4]. Contemporary MS techniques coupled with HPLC separation permit the rapid analysis of complex natural peptide libraries [5][6][7].…”

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confidence: 99%

Sequencing of T-superfamily conotoxins from Conus virgo: Pyroglutamic acid identification and disulfide arrangement by MALDI mass spectrometry

Mandal

Ramasamy

Sabareesh

et al. 2007

J. Am. Soc. Mass Spectrom.

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“…As a part of the comprehensive program for the identification and characterization of peptides from cone snails found in the Indian coastal seas (Sudarslal et al, 2003(Sudarslal et al, , 2004Gowd et al, 2005;Sabareesh et al, 2006;Mandal et al, 2007;Kallol et al, 2010), a molluscivorous cone snail endemic to India, C. araneosus was undertaken for this study. This species is restricted to shallow coastal seas of the southeast India and Sri Lanka (R€ ockel et al, 1995;Franklin et al, 2009).…”

Section: Introductionmentioning

confidence: 99%