Rock squirrel (Spermophilus variegatus) blood sera affects proteolytic and hemolytic activities of rattlesnake venoms

Biardi, James E.; Coss, Richard G.

doi:10.1016/j.toxicon.2010.12.011

Cited by 37 publications

(31 citation statements)

References 42 publications

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“…4). We speculate that such mutations may be important for sub-functionalization or increasing the potency of these proteins, or perhaps act as a weapon in the co-evolutionary arms race against prey resistance (61,62). A major proportion of the remaining variations in Echis SVMP were detected in the cysteine-rich and disintegrin-like domains (ϳ29%, ϭ 1.04 and 17%, ϭ 0.91, respectively).…”

Section: Discussionmentioning

confidence: 98%

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Brust

Sunagar

Undheim

et al. 2013

Molecular & Cellular Proteomics

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Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteinerich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type na- Snake venom metalloproteases (SVMP)1 evolved from ADAM (A disintegrin and metalloprotease) proteins that were recruited into the venom of snakes near the base of the advanced snake (Caenophidia) radiation. They have been identified in the venoms of all lineages of advanced snakes (1-5). The ancestral SVMP (P-III) contains (in downstream order) five domains: signal ϩ propeptide ϩ metalloprotease ϩ disintegrin ϩ cysteine rich. Following the divergence of vipers from the remaining caenophidians, extensive gene duplication, domain loss, and positive selection resulted in generation of the P-I and P-II classes of SVMP within the viperid lineage (6 -8). These two derived classes found in viper venoms lack either the cysteine-rich domain (P-II) or the cysteinerich and disintegrin domains (P-I) (8, 9). The signal peptide and the propeptide domain are typically cleaved off before expression although the latter has been detected in venoms on occasion (9). SVMP are often the dominant venom component in the venom of viperid snakes, but are typically much less significant in the venom of other snake families (10 -15). The majority of SVMP principally exhibit hemorrhagic activity, although other functions, such as the activation of prothrombin and Factor X, fibrin(ogen)olysis, apoptosis and the inhibition of platelet aggregation, have also been reported (16). Although SVMP-induced hemorrhage is primarily dependent on the proteolytic activity of the metalloprotease domain, the potency of this activity is incr...

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Section: Discussionmentioning

confidence: 98%

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Brust

Sunagar

Undheim

et al. 2013

Molecular & Cellular Proteomics

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“…A number of these enzymes are toxic (molecular weight ranges between 13 -150 kDa) and serve specific functions that include immobilizing, killing, and predigesting prey [4]. Snake venom phospholipases A 2 (svPLA 2 s) are highly abundant toxins having functional diversity and systemic toxicities including myotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, hepatotoxicity, neprotoxicity, reprotoxicity, and systemic hemorrhage [5][6][7][8][9]. These proteins induce release of inflammatory mediators [10], vasodilating and vasoconstricting mediators such as prostaglandins, histamine, kinins, eicosanoids, platelet activating factor, catecholamines, dopamine, nitric oxide and endothelins.…”

Section: Introductionmentioning

confidence: 99%

Snake Venom Phospholipases A2: A Novel Tool Against Bacterial Diseases

Samy¹,

Gopalakrishnakone²,

Stiles³

et al. 2012

Current Medicinal Chemistry

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The majority of snake venom phospholipases A(2) (svPLA(2)s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β-sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium- dependent catalytic mechanism. Additionally, svPLA(2)s display an array of biological actions that are either dependent or independent of catalysis. The PLA(2)s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gram-negatives by svPLA(2) requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic- based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA(2)s, which include "fatal depolarization" of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA(2)s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA(2)-derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA(2)s is bactericidal. Thus identification of the bactericidal sites in svPLA(2)s has potential for developing novel antimicrobials.

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“…Rock squirrels (Spermophilus variegatus), another North American sciurid, also have natural inhibition in their sera against rattlesnake venom's digestive and hemostatic activities (Biardi and Coss, 2010). S. variegatus is similar to S. beecheyi and X. inauris in its approach and harassment of venomous snakes (Owings et al, 2001).…”

mentioning

confidence: 99%

“…S. variegatus is similar to S. beecheyi and X. inauris in its approach and harassment of venomous snakes (Owings et al, 2001). Unlike S beecheyi (and similar to X. inauris) S. variegatus is exposed to multiple venomous species throughout its range to which they show multiple resistances (Biardi and Coss, 2010). Several mongoose species (Herpestidae) have venom resistances.…”

mentioning

confidence: 99%

“…However, they would still need to minimize the tissue destruction that follows envenomation from both species in order to maintain competitiveness against conspecifics and avoid predation (Biardi et al, 2005). Research on how ground squirrels respond to venom toxins physiologically helps clarify the risks to squirrels in snake and squirrel interactions (Biardi and Coss 2010). The lack of proteolytic resistance in X. inauris increases the risk of mobbing venomous snakes.…”

mentioning

confidence: 99%

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No evidence for proteolytic venom resistance in southern African ground squirrels

Phillips

Waterman

Plessis³

et al. 2012

Toxicon

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Many species that interact with venomous snakes show resistances to their venoms. The family Sciuridae has several North American members that harass venomous snakes and show proteolytic resistances in their sera. We examined sera collected from an African ground squirrel (Xerus inauris) against two sympatric venomous snakes (Bitis arietans and Naja annulifera) and found no support for proteolytic resistance. Our results add to our understanding of the risks in predator defense within the family Sciuridae.

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Rock squirrel (Spermophilus variegatus) blood sera affects proteolytic and hemolytic activities of rattlesnake venoms

Cited by 37 publications

References 42 publications

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Snake Venom Phospholipases A2: A Novel Tool Against Bacterial Diseases

No evidence for proteolytic venom resistance in southern African ground squirrels

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