Phylogenetic specificity of cholinergic ligands: .alpha.-conotoxin SI

Zafaralla, Glenn; Ramilo, Cecilia A.; Gray, William R.; Karlstrom, Rolf O.; Olivera, Baldomero M.; Cruz, Lourdes J.

doi:10.1021/bi00418a065

Cited by 106 publications

(80 citation statements)

References 15 publications

(15 reference statements)

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“…These IV samples contained peptides that were previously characterized from the DV of this species, including the calcium-channel blocker ω-SVIA (Ramilo et al, 1992) and nicotinic acetylcholinereceptor blockers α-SI and α-SII (Ramilo et al, 1992;Zafaralla et al, 1988), as confirmed by MALDI-MS. Interestingly, neither s4a nor s4b were observed components of the IV from these snails.…”

Section: Variation In the Composition Of Injected Venom Inmentioning

confidence: 96%

“…It is apparent both by the number of peaks that appear in the chromatograms, and the masses labeled, that IV is by no means identical to DV and contains a small subset of DV peptides, primarily less hydrophobic ones. Identifiable DV and IV peptides were fully processed from their propeptides and contained the known post-translational modifications such as carboxy-terminal amidation (s4a, ω-SVIB and α-SI) and proline hydroxylation (s4a and ω-SVIA; Craig et al, 1998;Ramilo et al, 1992;Zafaralla et al, 1988). Peptides s4a and s4b were also modified by O-glycosylation and pyroglutamylation (Craig et al, 1998).…”

Section: Comparison Of Duct Venom and Injected Venom Samples Inmentioning

confidence: 99%

“…Identification of well-known conopeptides by such a mass-matching approach has been used in another report . Since ω-SVIA, ω-SVIB (Ramilo et al, 1992), α-SI, α-SII (Ramilo et al, 1992;Zafaralla et al, 1988) and s4a (Craig et al, 1998) are well-characterized C. striatus peptides, an observed mass within 0.5·Da of the predicted value is sufficient to identify the peptides, and based on this criterion, these peptides were identified. We also determined mass matches based on ESI-MS and MALDI-MS data to within 0.5·Da for three putative peptides by using the calculated molecular masses with expected post-translational modifications predicted from published cDNA sequences.…”

Section: Identification Of Putative Conopeptides In Conus Striatusmentioning

confidence: 99%

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Intraspecific variation of venom injected by fish-hunting Conussnails

Jakubowski

Kelley

Sweedler

et al. 2005

Journal of Experimental Biology

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SUMMARY Venom peptides from two species of fish-hunting cone snails (Conus striatus and Conus catus) were characterized using microbore liquid chromatography coupled with matrix-assisted laser desorption/ionization-time of flight-mass spectrometry and electrospray ionization-ion trap-mass spectrometry. Both crude venom isolated from the venom duct and injected venom obtained by milking were studied. Based on analysis of injected venom samples from individual snails, significant intraspecific variation (i.e. between individuals) in the peptide complement is observed. The mixture of peptides in injected venom is simpler than that in the crude duct venom from the same snail, and the composition of crude venom is more consistent from snail to snail. While there is animal-to-animal variation in the peptides present in the injected venom, the composition of any individual's injected venom remains relatively constant over time in captivity. Most of the Conus striatus individuals tested injected predominantly a combination of two neuroexcitatory peptides (s4a and s4b),while a few individuals had unique injected-venom profiles consisting of a combination of peptides, including several previously characterized from the venom duct of this species. Seven novel peptides were also putatively identified based on matches of their empirically derived masses to those predicted by published cDNA sequences. Profiling injected venom of Conus catus individuals using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry demonstrates that intraspecific variation in the mixture of peptides extends to other species of piscivorous cone snails. The results of this study imply that novel regulatory mechanisms exist to select specific venom peptides for injection into prey.

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Section: Variation In the Composition Of Injected Venom Inmentioning

confidence: 96%

Section: Comparison Of Duct Venom and Injected Venom Samples Inmentioning

confidence: 99%

Section: Identification Of Putative Conopeptides In Conus Striatusmentioning

confidence: 99%

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Intraspecific variation of venom injected by fish-hunting Conussnails

Jakubowski

Kelley

Sweedler

et al. 2005

Journal of Experimental Biology

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“…A well defined subgroup of ␣-conotoxins, referred to as the ␣3/5 2 subfamily conotoxins (Table I), are antagonists of neuromuscular receptors and show, except for ␣-conotoxin SI (9,10), binding preference to the ␣ 1 /␥ subunit interface of Torpedo nAChR. On the other hand, more recently found ␣A-conotoxins differ from the ␣3/5 subfamily conotoxins in the amino acid sequences (11,12) as well as in their threedimensional structures (13).…”

mentioning

confidence: 99%

Solution Conformation of α-Conotoxin EI, a Neuromuscular Toxin Specific for the α1/δ Subunit Interface of Torpedo Nicotinic Acetylcholine Receptor

Park¹,

Suk²,

Jacobsen³

et al. 2001

Journal of Biological Chemistry

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A high resolution structure of ␣-conotoxin EI has been determined by 1 H NMR spectroscopy and molecular modeling. ␣-Conotoxin EI has the same disulfide framework as ␣4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the ␣3/5 and ␣A conotoxins. The unique binding preference of ␣-conotoxin EI to the ␣ 1 /␦ subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various ␣-conotoxins possessing distinct receptor subtype specificities. Structural comparison of ␣-conotoxin EI with the ␥-subunit favoring ␣-conotoxin GI suggests that the Torpedo ␦-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven ␣-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is ϳ20 Å (height) ؋ 20 Å (width) ؋ 15 Å (thickness).The nicotinic acetylcholine receptors (nAChRs) 1 are a well studied family of ligand-gated ion channels comprising a diverse set of molecular subtypes (1). The best characterized is the receptor at the neuromuscular junction, with four different subunits in a pentameric array, i.e. (␣ 1 ) 2 ␤ 1␥ ␦. Less well understood and more diverse are the neuronal nAChRs that assemble in exogenous expression systems with a general composition of (␣ m ) 2 (␤ n ) 3 , where m ϭ 2-6 and n ϭ 2-4, or (␣ 7 ) 5 (2, 3). A large variety of ligands bind to such diverse nAChRs via unknown mechanisms. A better understanding of the ligandbinding mechanism would be possible if a suitable three-dimensional structure of nAChR were available. Although cryoelectron microscopic images of nAChR show the spatial arrangement of five subunits of the receptor and some aspects of the ligand-binding pockets (4, 5), they are as yet insufficient for describing ligand-receptor interactions in atomic detail. In this regard, the recently determined crystal structure of acetylcholine-binding protein is expected to provide useful insight into ligand-nAChR interactions (6).Small peptide toxins of Conus origin known as the ␣-and ␣A-conotoxins are highly useful tools for exploring ligandnAChR interactions (7,8). A well defined subgroup of ␣-conotoxins, referred to as the ␣3/5 2 subfamily conotoxins (Table I), are antagonists of neuromuscular receptors and show, except for ␣-conotoxin SI (9, 10), binding preference to the ␣ 1 /␥ subunit interface of Torpedo nAChR. On the other hand, more recently found ␣A-conotoxins differ from the ␣3/5 subfamily conotoxins in the amino acid sequences (11, 12) as well as in their threedimensional structures (13). The ␣A-conotoxins, nevertheless, target neuromuscular receptors. A third subfamily of ␣-conotoxins known as the ␣4/7 subfamily has also been found; members of this subfamily target subtypes of neuronal and muscle nAChRs (14 -17). The ␣4/7 subfamily contains two disulfide bonds like the ␣3/5 subfamily but has a different spacing between the disulfide bonds.Even though a high resolutio...

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“…1 The majority of ␣-conotoxins isolated from fishhunting cone snails, including GI, GIA, and GII from Conus geographus (4), MI from Conus magus (5), and SI and SII from Conus striatus (6,7), show extensive structural homology, a conserved cysteine framework, and target the muscle subtype of the nAChR. The ␣-conotoxins PnIA and PnIB from a molluschunting cone snail, Conus pennaceus (8), and ImI from a wormhunting cone snail, Conus imperialis (9) share a similar cysteine framework to ␣-conotoxins from fish-hunting cones, but have a different sequence pattern and target the neuronal subtypes of the nAChR.…”

mentioning

confidence: 99%

α-Conotoxin EpI, a Novel Sulfated Peptide from Conus episcopatusThat Selectively Targets Neuronal Nicotinic Acetylcholine Receptors

Loughnan

Bond

Atkins

et al. 1998

Journal of Biological Chemistry

109

100

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We have isolated and characterized ␣-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus. The peptide was classified as an ␣-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previously described ␣-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from previously reported conotoxins in that it has a sulfotyrosine residue, identified by amino acid analysis and mass spectrometry. Native EpI was shown to coelute with synthetic EpI. The peptide sequence is consistent with most, but not all, recognized criteria for predicting tyrosine sulfation sites in proteins and peptides.

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Phylogenetic specificity of cholinergic ligands: .alpha.-conotoxin SI

Cited by 106 publications

References 15 publications

Intraspecific variation of venom injected by fish-hunting Conussnails

Intraspecific variation of venom injected by fish-hunting Conussnails

Solution Conformation of α-Conotoxin EI, a Neuromuscular Toxin Specific for the α1/δ Subunit Interface of Torpedo Nicotinic Acetylcholine Receptor

α-Conotoxin EpI, a Novel Sulfated Peptide from Conus episcopatusThat Selectively Targets Neuronal Nicotinic Acetylcholine Receptors

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