Cloning of an Unusual Natriuretic Peptide from the South American Coral Snake <i>Micrurus corallinus</i>

Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated.

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“…Natriuretic peptides have subsequently been discovered in a variety of elapid and crotalid venoms [95,140,141,142,143]. …”

Section: Resultsmentioning

confidence: 99%

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Aird

Silva

Qiu

et al. 2017

Toxins

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“…These NPs were noted to have long C-terminal extensions containing proline residues [105,106], which are features shared by DNP [5]. Among the 3 NPs (TNP-a, TNP-b, and TNP-c) isolated from the inland taipan, TNP-c was of similar potency to ANP and DNP, resulting in near complete relaxation in pre-contracted aortae [105].…”

Section: Dendroaspis Natriuretic Peptide and Other Snake Venomsmentioning

confidence: 99%

“…Novel NPs have also been isolated from Oxyuranus microlepidotus (the inland taipan), [105] and Micrurus corallinus (the South American coral snake) [106]. These NPs were noted to have long C-terminal extensions containing proline residues [105,106], which are features shared by DNP [5].…”

Section: Dendroaspis Natriuretic Peptide and Other Snake Venomsmentioning

confidence: 99%

Natriuretic peptides and therapeutic applications

2007

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Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.

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“…45 In isolated renal perfusion studies, Russell's viper venom reduced the potential difference across the cell membrane of proximal tubule cells and decreased the tubular reabsorption of sodium in a dose-dependent fashion. 46,47 Peptides present in the venom of the Eastern green mamba snake (Dendroaspis angusticeps), 48 the South American coral snake (Micrurus corallinus) 49 and the jararaca pit viper 50 can cause natriuresis by decreasing sodium reabsorption in the distal nephron, through activation of cyclic GMP. The direct glomerular injury and renal tubule effects associated with snake bite are not thought to cause AKI by themselves.…”

Section: Pathophysiologymentioning

confidence: 99%

Animal toxins and the kidney

Sitprija

2008

Nat Rev Nephrol

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Envenomation or poisoning by toxins from animals poses an important health hazard in the tropics. Animal toxins are complex mixtures of proteins, peptides, enzymes and chemicals. These toxins exert their effects through modulation of ion channels and receptors, and via direct enzyme action. Depolarization or hyperpolarization of ion channels--caused by most marine toxins, and some snake and insect venoms--results in neuromuscular symptoms that can be associated with hemodynamic changes. Toxin enzymes, especially proteases and phospholipase A2, initiate inflammatory processes that involve the generation of proinflammatory cytokines and vasoactive mediators, resulting in systemic and renal hemodynamic alterations. Toxin enzymes also have direct effects on erythrocytes, myocytes, blood coagulation factors, vascular endothelium and epithelial cells. As a result, disseminated intravascular coagulation, bleeding diathesis, intravascular hemolysis and rhabdomyolysis are common after exposure to animal toxins. The renal manifestations of animal toxin envenomation, which are usually acute, result mainly from these enzymatic effects. All renal structures can be affected by animal toxins, and tubular necrosis is common. Acute kidney injury is attributed to decreased renal blood flow (associated with intravascular hemolysis or rhabdomyolysis), disseminated intravascular coagulation or direct tubular toxicity. Immunologic mechanisms have a minor role in the pathophysiology of nephropathy caused by animal toxins.

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Cloning of an Unusual Natriuretic Peptide from the South American Coral Snake Micrurus corallinus

Cited by 42 publications

References 30 publications

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

Natriuretic peptides and therapeutic applications

Animal toxins and the kidney

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