Isolation of a Member of the Neurotoxin/Cytotoxin Peptide Family from Xenopus laevis Skin Which Activates Dihydropyridine-sensitive Ca2+ Channels in Mammalian Epithelial Cells

Macleod, John; Lembessis, Peter; James, Susan; Bennett, H. P. J.

doi:10.1074/jbc.273.32.20046

Cited by 11 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sequence of X. tropicalis originates from DNA sequencing and evidence at protein level or function is not known yet. The similarity with the xenoxins previously shown to be present in the skin secretion of X. laevis [ 33 , 34 ] is much lower (Figure 5d ). Interestingly, the prototype and other described members of this family of 3-finger toxin proteins are all known to be composed of a single polypeptide chain.…”

Section: Resultssupporting

confidence: 63%

Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping

Oosten

Pieterse

Pinkse

et al. 2015

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain disulfide bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter- and intra-molecular disulfide bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the sulfur atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between cysteine-containing peptides and peptides lacking sulfur. High sulfur content in a peptide decreases the normalized nominal mass defect (NMD) and increases the normalized isotopic shift (NIS). Hence in a 3D plot of mass, NIS, and NMD, peptides with sulfur appear in this plot with a distinct spatial localization compared with peptides that lack sulfur. In this study we investigated the skin secretion of two frog species; Odorrana schmackeri and Bombina variegata. Peptides from the crude skin secretions were separated by nanoflow LC, and of all eluting peptides high resolution zoom scans were acquired in order to accurately determine both monoisotopic mass and average mass. Both the NMD and the NIS were calculated from the experimental data using an in-house developed MATLAB script. Candidate peptides exhibiting a low NMD and high NIS values were selected for targeted de novo sequencing, and this resulted in the identification of several novel inter- and intra-molecular disulfide bond containing peptides.Graphical AbstractᅟElectronic supplementary materialThe online version of this article (doi:10.1007/s13361-015-1282-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultssupporting

confidence: 63%

Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping

Oosten

Pieterse

Pinkse

et al. 2015

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…TSA-1 is structurally related to a number of Ly-6 superfamily molecules known to directly bind and regulate the activity of plasma membrane ion channels, including xenoxin-1 (14), calciseptine (7), and caltrin (6). While there is presently no evidence that TSA-1 acts at the level of plasma membrane ion channels, it is significant that MAb blockade of TSA-1 interferes with Ca 2ϩ -dependent cellular responses in T cells, such as IL-2 secretion (11,22).…”

Section: Discussionmentioning

confidence: 99%

Essential Role for the Lymphostromal Plasma Membrane Ly-6 Superfamily Molecule Thymic Shared Antigen 1 in Development of the Embryonic Adrenal Gland

Zammit¹,

Berzins²,

Gill³

et al. 2002

Molecular and Cellular Biology

View full text Add to dashboard Cite

Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system. TSA-1 is also expressed in other nonhematopoietic tissues, in particular, embryonic and adult adrenal glands. To address the function of TSA-1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting. Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities. We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline. We conclude that TSA-1 is required for normal embryonic development but that deletion of its expression does not obviously impair lymphoid development.

show abstract

“…Other TFPs activate Ca 2+ channels in epithelial cells (e.g. xenoxin [13]), or enhance sperm motility by inhibiting Ca 2+ transport into spermatozoa (e.g. SVS-VII ⁄ caltrin [14]).…”

mentioning

confidence: 99%

Plethodontid modulating factor, a hypervariable salamander courtship pheromone in the three‐finger protein superfamily

et al. 2007

View full text Add to dashboard Cite

The proteins in the three-finger protein superfamily are highly variable but all share a relatively simple structure termed a 'three-finger' fold. This three-dimensional structure consists of three adjacent 'finger-like' loops extending from a small, hydrophobic core that is cross-linked by a common disulfide bond bridging pattern (see review [1]). The three-finger proteins (TFPs) are widespread, and both soluble and membranebound members have been described in detail (refer to [1][2][3] for original references).TFPs have very diverse functions and exhibit an extraordinary degree of tissue and taxon specificity [4]. This functional diversity is well illustrated within families of TFPs, such as the family of three-finger toxins The soluble members of the three-finger protein superfamily all share a relatively simple 'three-finger' structure, yet perform radically different functions. Plethodontid modulating factor (PMF), a pheromone protein produced by the lungless salamander, Plethodon shermani, is a new and unusual member of this group. It affects female receptivity when delivered to the female's nares during courtship. As with other plethodontid pheromone genes, PMF is hyperexpressed in a specialized male mental (chin) gland. Unlike other plethodontid pheromone genes, however, PMF is also expressed at low levels in the skin, liver, intestine and kidneys of both sexes. The PMF sequences obtained from all tissue types were highly variable, with 103 unique haplotypes identified which averaged 35% sequence dissimilarity (range 1-60%) at the protein level. Despite this variation, however, all PMF sequences contained a conserved 20-amino-acid secretion signal sequence and a pattern of eight cysteines that is also found in cytotoxins and short neurotoxins from snake venoms, as well as xenoxins from Xenopus. Although they share a common cysteine pattern, PMF isoforms differ from other three-finger proteins in: (a) amino-acid composition outside of the conserved motif; (b) length of the three distinguishing 'fingers'; (c) net charge at neutral pH. Whereas most three-finger proteins have a net positive charge at pH 7.0, PMF has a high net negative charge at neutral pH (pI range of most PMFs 3.5-4.0). Sequence comparisons suggest that PMF belongs to a distinct multigene subfamily within the threefinger protein superfamily.Abbreviations ISH, in situ hybridization; nAChR, nicotinic acetylcholine receptor; PMF, plethodontid modulating factor; PRF, plethodontid receptivity factor; TFP, three-finger protein; VNO, vomeronasal organ.

show abstract

Isolation of a Member of the Neurotoxin/Cytotoxin Peptide Family from Xenopus laevis Skin Which Activates Dihydropyridine-sensitive Ca2+ Channels in Mammalian Epithelial Cells

Cited by 11 publications

References 31 publications

Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping

Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping

Essential Role for the Lymphostromal Plasma Membrane Ly-6 Superfamily Molecule Thymic Shared Antigen 1 in Development of the Embryonic Adrenal Gland

Plethodontid modulating factor, a hypervariable salamander courtship pheromone in the three‐finger protein superfamily

Contact Info

Product

Resources

About